Papovaviruses are a family of small, non-enveloped viruses with circular double-stranded DNA genomes. The family includes the genera Papillomavirus and Polyomavirus. Papillomaviruses can cause warts and some strains are associated with cancers like cervical cancer. Polyomaviruses can cause diseases in immunocompromised individuals like progressive multifocal leukoencephalopathy. Both viruses establish latent, lifelong infections and have oncogenic properties through viral proteins that interact with host cell growth regulators.
Poxviruses are brick or oval-shaped viruses with large double-stranded DNA genomes. Poxviruses exist throughout the world and cause disease in humans and many other types of animals. Poxvirus infections typically result in the formation of lesions, skin nodules, or disseminated rash.
Largest viruses that infect vertebrates
Can be seen under light microscope
Poxvirus diseases are characterized by skin lesions – localized or generalized
Important diseases caused by poxviruses are-
Smallpox
Monkeypox
Cowpox
Tanapox
Molluscum contagiosum
The Paramyxoviridae is a family of single-stranded RNA viruses known to cause different types of infections in vertebrates. Examples of these infections in humans include the measles virus, mumps virus, parainfluenza virus, and respiratory syncytial virus (RSV).
Adenoviridae is a group of medium sized, non-enveloped, double stranded DNA viruses that replicate and produce disease in the eye and in the respiratory, gastrointestinal and urinary tracts;
Poxviruses are brick or oval-shaped viruses with large double-stranded DNA genomes. Poxviruses exist throughout the world and cause disease in humans and many other types of animals. Poxvirus infections typically result in the formation of lesions, skin nodules, or disseminated rash.
Largest viruses that infect vertebrates
Can be seen under light microscope
Poxvirus diseases are characterized by skin lesions – localized or generalized
Important diseases caused by poxviruses are-
Smallpox
Monkeypox
Cowpox
Tanapox
Molluscum contagiosum
The Paramyxoviridae is a family of single-stranded RNA viruses known to cause different types of infections in vertebrates. Examples of these infections in humans include the measles virus, mumps virus, parainfluenza virus, and respiratory syncytial virus (RSV).
Adenoviridae is a group of medium sized, non-enveloped, double stranded DNA viruses that replicate and produce disease in the eye and in the respiratory, gastrointestinal and urinary tracts;
Adenoviruses (members of the family Adenoviridae) are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from their initial isolation from human adenoids in 1953.
The presentation includes disease, treatment and management.
A picornavirus is a virus belonging to the family Picornaviridae, a family of viruses in the order Picornavirales. Vertebrates, including humans, serve as natural hosts. Picornaviruses are nonenveloped viruses that represent a large family of small, cytoplasmic, plus-strand RNA viruses with a 30-nm icosahedral capsid.
The Epstein–Barr virus (EBV), also called human herpesvirus 4 (HHV-4), is one of eight known human herpesvirus types in the herpes family, and is one of the most common viruses in humans.
Viral classification and Types of Replication in virus Rakshith K, DVM
Precise presentation on Viral classification and Types of replication in Virus.
Entry of virus
Spread of virus
General steps in a virus replication cycle
Attachment, Penetration, Uncoating, Multiplication
Multiplication of Single-Stranded RNA (ss RNA) Viruses
Multiplication of Double-Stranded RNA (ds RNA) Viruses
Multiplication of Single-Stranded DNA (ss DNA) Viruses
Multiplication of Double-Stranded DNA (ds DNA) Viruses
Release of new virions
Common viral diseases of Bovines
Adenoviruses (members of the family Adenoviridae) are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from their initial isolation from human adenoids in 1953.
The presentation includes disease, treatment and management.
A picornavirus is a virus belonging to the family Picornaviridae, a family of viruses in the order Picornavirales. Vertebrates, including humans, serve as natural hosts. Picornaviruses are nonenveloped viruses that represent a large family of small, cytoplasmic, plus-strand RNA viruses with a 30-nm icosahedral capsid.
The Epstein–Barr virus (EBV), also called human herpesvirus 4 (HHV-4), is one of eight known human herpesvirus types in the herpes family, and is one of the most common viruses in humans.
Viral classification and Types of Replication in virus Rakshith K, DVM
Precise presentation on Viral classification and Types of replication in Virus.
Entry of virus
Spread of virus
General steps in a virus replication cycle
Attachment, Penetration, Uncoating, Multiplication
Multiplication of Single-Stranded RNA (ss RNA) Viruses
Multiplication of Double-Stranded RNA (ds RNA) Viruses
Multiplication of Single-Stranded DNA (ss DNA) Viruses
Multiplication of Double-Stranded DNA (ds DNA) Viruses
Release of new virions
Common viral diseases of Bovines
Genital warts are an epidermal manifestation attributed to the epidermotropic human papillomavirus (HPV).
> than 100 types of double-stranded HPV papovaviruses have been isolated thus far, and, of these, about 35 types have affinity to genital sites
The presentation covers all major aspects of the virus including oncogenicity, Structure, Pathogenesis. It also covers preventive measures and vaccines. This presentation is targeted to students at bachelors level for allied/optional microbiology paper
HPV can cause cervical and other cancers, including cancer of the vulva, vagina, penis, or anus. It can also cause cancer in the back of the throat (called oropharyngeal cancer). This can include the base of the tongue and tonsils. Cancer often takes years, even decades, to develop after a person gets HPV.
Slideshow is from the University of Michigan Medical
School's M1 Infectious Disease / Microbiology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1IDM
Human Papilloma Virus AND CERVICAL CANCER.pptxShraddhaDubey29
WHAT IS HPV?
Human pappiloma virus is double stranded dna virus that infect the epithelial cells of skin and mucous.
The epithelial surface includes all areas covered by skin and/or mucous such as the cervix,vagina,penis,anus,mouth,throat,tounge and tonsil.
Reffered to papillomavirus as certain type may cause bening, skinwarts or papilloma.
Human pappiloma virus is the most commom viral infection of reproductive tract. Hpv is sexually transmitted but penetrative sex is not required for transmission. Skin to skin genital contact is a well recogonised mode of transmission. There are many type of hpv and many do not cause problemes. Hpv infection usually clear up without any intervention within a few month after acquisition and about 90% clear within 2 year. A all proportion of infection with certain types of hpv can persist and progress to cervical cancer.
PATHOGENSIS
Establishment of HPV infection requires damage to the surface epithelium, which allows the virus access to the immature cells in the basal layer epithelium. Normally mature squamous cells are arrested in the g1 phase of the cell cycle but they continue to actively progress throughthe cell cycle when infected with HPV which uses the host cell dna synthesis machinery to replicate its own genome.Normal cells have basal epithelial cells, intermediate cells, superficial cells. HPV doesn’t infect superficial cell there should be break in surface epithelium so it has an acess to the basal cells. So once it infect the basal cell the dna of the hpv enter in the nucleus and it doesn’t integrate into the host chromosome it remain as a circular episomal dna . as the cell proliferate it also proliferate and it produces viral protein E1,E2. AS the proliferation increases it produces E1,E2,E3,E4,E5,E6,E7. Then finally it start producing L1 and L2 protein this re capsid protein . once they are produced the viral assembly occurs and the virions are released outside
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
2. Family papovaviridae comprises two genera:
The genus Papillomavirus,
containing the many papillomaviruses of mammals and birds,
• The genus Polyomavirus,
containing a few pathogens of animals and humans.
The first two syllables of the name Papovaviridae refer to the genera
Papillomavirus and Polyomavirus; "va" alludes to "vacuolating agent," an old
name for the prototype polyomavirus, simian virus 40 (SV40).
The family of Papovaviridae is no longer used in recent taxonomy, but is
split into the Papillomaviridae and the Polyomaviridae
Papovaviruses
3. • Virions are non enveloped, spherical in outline, with icosahedral
symmetry.
• Virions are 55 (genus Papillomavirus) or 45 (genus Polyomavirus) nm in
diameter
• The genome : circular double stranded DNA.
• The DNA has covalently closed ends, is circular and supercoiled and is
infectious
• 8 (genus Papillomavirus)or 5 (genus Polyomavirus) kbp in size.
• Members of both genera replicate in nucleus
• Members of the genus Polyomavirus grow in cultured cells whereas,
members of the genus Papillomavirus have not been grown in culture.
4. • During replication, polyomavirus DNA is transcribed from both
strands, whereas papillomavirus DNA is transcribed from one
strand.
• Viruses encode proteins that promote cell growth by binding to
the cellular growth-suppressor proteins p53 and p105RB.
• Viruses can cause lytic infections in permissive cells but cause
abortive, persistent, or latent infections in non permissive cells.
Note:
• Permissive cells are cells that can support the growth of a virus.
5.
6.
7. Replication
• Virions attach to cellular receptors, enter via receptor-mediated
endocytosis, and are transported to the nucleus where they are uncoated,
releasing their DNA.
• During productive infection, transcription of the viral genome is divided
into early and late stages.
• Transcription of early and late coding regions is controlled by separate
promoters and occurs on opposite DNA strands in the case of
polyomaviruses and on the same strand with papillomaviruses.
8. • First, the half of the genome that contains the early genes is transcribed,
forming mRNAs that direct the synthesis of enzymes involved in viral
replication.
• Late mRNAs that direct the synthesis of virion structural proteins are
transcribed from the other half of the viral genome after DNA synthesis has
begun.
• Progeny DNA molecules serve as additional template, amplifying the
production of structural proteins greatly.
• Several different translational strategies are employed to enhance the
limited coding capacity of the viral genomes.
9. • Papovavirus DNA replication begins at a single unique origin of
replication and proceeds bidirectional.
• Virions are assembled in the nucleus and are released on cell death,
often just as a consequence of cellular replacement in epithelia.
• Some cells exhibit a characteristic cytopathic effect, marked by
cytoplasmic vacuolization.
• An infected cell may produce 10,000 to 100,000 virions.
12. • HPV infection is highly species/tissue specific, infecting only the cutaneous
and mucosal epithelia of the anogenital tract (Angiogenital tract is a term
used to refer to both the anus and genital tract) or upper respiratory tract .
• Transmission of HPV is believed to be through minor abrasions of the
epithelium which expose cells in the basal layer for viral entry.
• Although heparin sulfate is suggested to be the mediator for the initial viral
entry, the identity of the HPV receptor is still unknown.
• Primary HPV infection always begins in the cells of the basal layer of
squamous epithelium, where the virus maintains its genome as low-copy
episomal DNA.
13. • HPV late gene expression and
virion production only occur
in the nucleus of terminally
differentiated keratinocytes.
• (A keratinocyte is the
predominant cell type in the
epidermis, the outermost
layer of the skin, constituting
90% of the cells found there.)
• Hence the vegetative HPV
DNA production is tightly
controlled by keratinocyte
differentiation.
14. The circular double-stranded DNA genome
of HPV, about 8 kb in size, is composed of
three regions:
• a non-coding upstream regulatory region
(URR) containing transcription promoters
and DNA replication elements;
• an early region encoding six proteins
(E1, E2,E4, E5, E6 and E7); and a late
region encoding two capsid proteins (L1
and L2).
15. • Most HPV genes are transcribed as polycistronic mRNAs from a single
DNA strand.
• HPV uses alternate RNA splicing and alternative RNA polyadenylation
to ensure the proper expression of all open reading frames (ORFs)
from a compact genome.
• Most HPV infections (90%) go away by themselves within two years.
16. • If HPV infections persists , can cause a variety of serious health problems
that include:
• Genital warts.
• Recurrent Respiratory Papillomatosis (RRP), a rare condition in which
warts grow in the throat.
• Cervical cancer.
• Other, less common, but serious cancers, including genital cancers
(cancer of the vulva, vagina, penis, or anus), and a type of head and neck
cancer called oropharyngeal cancer (cancer in the back of throat,
including the base of the tongue and tonsils).
17.
18.
19. • Based on their oncogenic
capability, papillomaviruses are
divided into high-risk and low-
risk groups.
• The high-risk groups consists of
HPV-16, 18, 31, 33, 35, 39, 45,
51,52, 56, 58, 59 ,66.
• low-risk groups includes HPV-6
and 11.
20. • There are more than 100 types of human papillomavirus (HPV).
• About 40 kinds can infect your genital area -
vulva, vagina, cervix, rectum, anus, penis, and scrotum — as well as your
mouth and throat.
• These kinds of HPV are spread during sexual contact.
• (Other types of HPV cause common warts like hand warts and plantar
warts on the feet — but these aren’t sexually transmitted.)
• Genital HPV infections are very, very common.
21. • In fact, most people who have sex get the HPV at some point in their lives.
• Most people with HPV have no symptoms and feel totally fine, so they
usually don’t even know they’re infected.
• Most genital HPV infections aren’t harmful at all and go away on their own.
• But some kinds of HPV can lead to genital warts or certain types of cancer.
• Two types of HPV (types 6 and 11) cause most cases of genital warts.
• But they’re considered low-risk HPV because they don’t lead to cancer or
other serious health problems.
22. • At least a dozen types of HPV can sometimes lead to cancer, though two
in particular (types 16 and 18) lead to the majority of cancer cases.
• These are called high-risk HPV.
• Cervical cancer is most commonly linked to HPV, but HPV can also cause
cancer in vulva, vagina, penis, anus, mouth, and throat.
23. LESIONS IN HUMANS CAUSED BY HPVs
LESIONS HPV TYPE COMMENT
Plantar warts 1
Common warts 2, 27, 29, 54; 4
Flat warts 3, 10, 28, 41
Butcher’s warts 7, 40 Common warts on the hands of
butchers
Reddish brown (macular) plaques
of epidermodysplasia
verruciformis
5, 8, 12, 14, 19-23, 25, 36, 46,
47, 49; 9, 15, 17; 37, 38; 24
May become malignant in light-
exposed areas
Anogenital warts (condyloma);
laryngeal papillomas
6, 11 Anogenital warts (vagina, vulva,
rarely the cervix, penis, anus,
perineum) are a commonly
transmitted disease; respiratory
papillomatosis, with malignant
transformation, is a rare disease
probably acquired at birth.
Cervical intraepithelial neoplasia
(CIN) and cervical cancer
- strong association
- moderate association
16, 18
31, 33, 35, 45, 51, 52, 56
Lower genital tract cancers
25. Diseases
Common Cutaneous Warts - “Verrucae vulgaris”
• Painless superficial medium-sized rough hyperkeratinized nodules at the site
of initial infection.
• Primarily occurs on the hands and fingers as well as on the feet
• May progress to deep palmo-plantar warts.
Cervical Intraepithelial Neoplasia “CIN”
• Benign neoplasm of the cervix
• May progress to cervical carcinoma Cervical Carcinoma
• Malignant neoplasm of the cervix Caused by progression of cervical
intraepithelial neoplasia
26. Deep Palmo-Plantar Warts “Myrmecias”
• Painful deep medium-sized rough hyperkeratinized pigmented
nodules at the site of initial infection.
• Primarily occurs on the feet and toes as well as on the hands
Caused by progression of common cutaneous warts
Anogenital Warts - “Condyloma acuminata”
• Multiple small papules coalescing to form a large cauliflower-like
lesion at the site of initial infection.
• Primarily occurs on the external genitalia or perirectally
32. Prevention
• Two vaccines (Cervarix and Gardasil) protect against cervical
cancers.
• One vaccine (Gardasil) also protects against genital warts and
cancers of the anus, vagina and vulva.
• Both vaccines are available for females, whereas Gardasil is
available for males
34. PolyomaVirus
• Poly= multiple & oma= tumor
• Circular genome of dsDNA.
• Family: Polyomaviridae
(formally grouped with papillomaviruses)
• Non-Enveloped, Naked Capsid.
• Icosahedral shape.
• Capsid: about 45nm(40-50nm) in diameter
35. • The name polyoma refers to the virus’s ability to produce multiple (
poly) tumors (oma).
• Clinically, Polyomaviridae are relevant as they contribute to pathologies
such as progressive multifocal leukoencephalopathy (JC virus),
nephropathy (BK virus) and Merkel cell cancer (Merkel cell virus).
• murine Polyomavirus was the first Polyomavirus discovered by Ludwik
Gross in 1953.
• Subsequently, many Polyomaviruses have been found to infect birds and
mammals.
36. • The Polyomaviruses have been extensively studied as tumor
viruses in humans and animals,
• leading to fundamental insights into carcinogenesis, DNA replication
and protein processing.
• Virus is probably acquired through the respiratory route spread
by viremia to the kidneys early in life.
• Infections are asymptomatic
• Virus establishes persistent and latent infection in organs such
as the kidneys and lungs.
37. Examples:
1-JC virus (JCV) /John Cunningham virus
• Causes progressive multifocal leukoencephalopathy (PML)
• Progressive demage or inflamation of white matter of brain at multiple
locations.
• Harmless except in cases of weakend immune system in AIDS
2-BK virus (BKV)
• Latent until immunosuppression occurs.
• Causes renal diseases in kidney transplanted patients
38. • BK virus (named for the patient’s initials): isolated in 1971 from the
urine of a renal allograft recipient with ureteric obstruction
• JC virus (also named for the patient’s initials): cultivated in 1971 from
the brain of a patient with progressive multifocal leukoencephalopathy
in the context of Hodgkin's disease KI virus (“Karolinska Institutet”):
identified 2007 using large-scale molecular virus screening method to
identify unrecognized human pathogens.
• WU virus (“Washington University”): identified 2007 from respiratory
secretions of patients with URI symptoms.
• MCV virus: found in Merkel cell carcinomas in 2008
39.
40.
41. Special Characteristics
• Persist as latent infections in a host without causing disease
• May produce tumor (Oncogenic)
Not the entire viral genome is transcribed in transformed cells but only the
portion of it that encodes the early functions, that is, the various tumor antigens
There are three non-capsid regulatory proteins: large T (T Ag), small t
and agnoprotein. Murine polyomaviruses have an additional middle T Ag.
(large T and small t antigens in the case of simian virus SV40 and large T,middle T
and small t antigens in the case of polyoma virus)
42. • These proteins are responsible for the induction and maintenance of
the transformed state
The large T antigen.
• the large T antigen stimulates host cell DNA synthesis, a function
that can be separated from its ability to initiate viral DNA
replication
• it is a transactive transcriptional activator capable of initiating
the transcription of inappropriate cellular genes
• these binds to the two cellular anti oncogene proteins p53 and
p110Rb which inactivates their growth suppressor
43. Middle T antigen.
• Role in enhancing full expression of the transformed phenotype;
expression of middle T antigen alone causes transformation to highly
tumorigenic cells.
• Since polyoma middle T antigen by itself is capable of fully transforming
cells, it is what is known as an acute transforming gene product
Small t antigen.
• Complements the functions of large T.
• It causes loss of contact inhibition, ability to produce increased amounts
of plasminogen activator and dissolution of intracellular actin cable
network
44. • The classification of Polyomaviruses is constantly evolving due to the
explosion of newly discovered viruses.
• Previously, the family of Polyomaviridae was divided into three major
clades; SV40 clade, avian clade and murine Polyomavirus clade.
• The recent reclassification by the International Committee on Taxonomy of
Viruses (ICTV) has recommended three genera as follow:
• Many of the known viruses have not been fully classified or have not yet
been officially accepted; hence, the taxonomy of this family is ongoing.
Genus Types Species
Orthopolyomavirus SV40
Wukipolyomavirus KI polyomavirus
Avipolyomavirus Avian polyomavirus
45. Genome organization:
• Closed, Circular, dsDNA genome
• Complexed with cellular histones.
• Encodes proteins/genes:
• VP1(Viral protein 1), VP2, VP3---form viral capsid
• Polyomavirus replicates in nucleus of host, host dependent-specific
46. • The genome is circular composed of double stranded DNA and encodes for 6
proteins;
• they are Large-T, small-T, viral protein 1 (VPl)/ viral protein 2 (VP2) and viral
protein 3 (VP3) 1— and agnoprotein.
• The agnoprotein is a small multifunctional phosphor-protein found in
the late coding part of the genome. It appears to be involved in DNA
replication but the exact mechanism remains unclear.
• Agnoprotein is a protein expressed by some members of the polyomavirus
family from a gene called the agnogene.
• Polyomaviruses in which it occurs include two human polyomaviruses
associated with disease, BK virus and JC virus, as well as the simian
polyomavirus SV40.
• It is about 5 kilobase pairs in length associated with cellular histones.
• VP 1-3 is responsible for the viral capsid formation.
47.
48. • Polyomaviruses are
unenveloped double-
stranded DNA viruses with
circular genomes of
around 5000 base pairs.
• The genome is packaged
in a viral capsid of about
40-50 nanometers in
diameter, which is
icosahedral in shape.
49. • The capsid is composed of 72 pentameric capsomeres of a protein
called VP1, which is capable of self-assembly into a closed
icosahedron; each pentamer of VP1 is associated with one molecule
of one of the other two capsid proteins, VP2 or VP3.
• The genome of a typical polyomavirus codes for between 5 and 9
proteins, divided into two transcriptional regions called the early and
late regions due to the time during infection in which they are
transcribed.
• Each region is transcribed by the host cell's RNA polymerase II as a
single pre-messenger RNA containing multiple genes.
• . The early region usually codes for two proteins, the small and large
tumor antigens, produced by alternative splicing.
• The late region contains the three capsid structural proteins VP1, VP2,
and VP3, produced by alternative translational start sites.
50.
51. Replication and life cycle
• The polyomavirus life cycle begins with entry into a host cell.
• Cellular receptors for polyomaviruses are sialic acid residues of glycans,
commonly gangliosides.
• The attachment of polyomaviruses to host cells is mediated by the binding
of VP1 to sialylated glycans on the cell surface.
• In some particular viruses, additional cell-surface interactions occur; for
example, the JC virus is believed to require interaction with the 5HT2A
receptor and the Merkel cell virus with heparan sulfate.
• After binding to molecules on the cell surface, the virion is endocytosed
and enters the endoplasmic reticulum
• the viral capsid structure is likely to be disrupted by action of host cell
disulfide isomerase enzymes.
52. • The details of transit to the nucleus are not clear and may vary among
individual polyomaviruses.
• Virion particle is released from the endoplasmic reticulum into the
cell cytoplasm, where the genome is released from the capsid,
possibly due to the low calcium concentration in the cytoplasm.
• Both expression of viral genes and replication of the viral genome
occur in the nucleus using host cell machinery.
• The early genes - comprising at minimum the small tumor antigen
(ST) and large tumor antigen (LT) - are expressed first.
• These proteins serve to manipulate the host's cell cycle -
dysregulating the transition from G1 phase to S phase, when the host
cell's genome is replicated - because host cell DNA replication
machinery is needed for viral genome replication.
53. • Expression of the late genes results in accumulation of the viral capsid
proteins in the host cell cytoplasm.
• Capsid components enter the nucleus in order to encapsidate new viral
genomic DNA. New virions may be assembled in viral factories.
• The mechanism of viral release from the host cell varies among
polyomaviruses; some express proteins that facilitate cell exit, such as the
agnoprotein or VP4.
• In some cases high levels of encapsidated virus result in cell lysis, releasing
the virions.
Genus Host details
Tissue
tropism
Entry details
Release
details
Replication
site
Assembly
site
Transmission
Polyomavirus
Mammals;
birds
Respiratory
system;
kidneys,
brain
Cell receptor
endocytosis
Lysis Nucleus Nucleus Oral-fecal
54.
55. • JC virus (JCV) life cycle in target cells.
1. JCV adhesion to receptors in target cells.
2. JCV internalization through clathrin mediated endocytosis and transport to the
early endosomes.
3. Transport to either recycling or late endosomes.
4. Virus transport in the endoplasmic reticulum up to the nucleus.
5. DNA replication in the nucleus.
6. Early gene transcription (regulatory genes).
7. Late gene transcription (structural genes).
8. Translation of the transcripts from either early or late genes.
9. Viral particles' assembly and virus release from target cells with either lytic
(oligodendrocytes) or nonlytic mechanisms (tubular epithelial cells).
56.
57. Transmission
• The mechanism of human-to-human transmission of the
polyomaviruses JC virus (JCV) and BK Virus (BKV) has not
been firmly established
58. Diseases
• Highly common childhood and young adult infections mostly cause little or
no symptoms.
• Lifelong persistence among almost all adults
• Most common among persons who become immunosuppressed by AIDS,
old age or after transplantation and include Merkel cell carcinoma (MCC) is
a rare and highly aggressive skin cancer) , PML and BK nephropathy
• Progressive multifocal leukoencephalopathy caused by reactivation of JC
virus Nephropathy (broad medical term used to denote disease or damage
of the kidney) and Merkel cell cancer (Merkel cell virus) caused by
reactivation of BK virus.
59. Merkel-cell carcinoma (MCC)
• is a rare and highly aggressive skin cancer, which, in most
cases, is caused by the Merkel cell polyomavirus (MCV).
• a rare potentially fatal skin tumor affecting older and
immunosuppressed individuals
60. Progressive multifocal leukoencephalopathy (PML)
• Progressive multifocal leukoencephalopathy (PML) is a deadly
demyelinative disease of the CNS due to lytic infection of
oligodendrocytes by the ubiquitous opportunistic polyoma virus JC(JCV).
• It is a rare and usually fatal viral disease characterized by progressive
damage (-pathy) or inflammation of the white matter (leuko-) of the brain
(-encephalo-) at multiple locations (multifocal).
• It is caused by the JC virus, which is normally present and kept under
control by the immune system. The JC virus is harmless except in cases of
weakened immune systems.
61.
62. Pathogenesis:
• The Polyomaviruses[JC virus (JCV), Bkvirus(BKV)and simian virus 40 (SV40)]
establish subclinical and persistent infections and share the capacity for
reactivation from latency in their host under immunosuppression.
• The JCV establishes latency mainly in the kidney and its reactivation results
in the development of progressive multifocal leukoencephalopathy.
• The BKV causes infection in the kidney and the urinary tract.
65. Epidemiology:
• The members of the Polyomavirus are found throughout the world in birds,
rodents, nonhuman primates, and of course, human populations.
• SV40 infects only Old World monkeys, and African and Indian macaques,
but interestingly not New World monkeys (e.g., owl and squirrel monkeys).
• Perhaps indicating a species barrier that is not completely understood.
• The epidemiologic data have been collected mostly on the BKV and JCV
because they are of human origin and cause widespread infections globally.
66. • Serological surveys of populations using hemagglutination inhibition
assays for the detection of antibodies indicates that seroconversion to
BKV takes place early in life, 5 to 7years, with conversion to JCV
occurring later.
• The virus is very common in the general population, infecting 70% to
90% of humans; most people acquire Human polyomavirus 2 in
childhood or adolescence.
• It is found in high concentrations in urban sewage worldwide, leading
some researchers to suspect contaminated water as a typical route of
infection
67. Laboratory Diagnosis of Polyomavirus (JC and BK
Infections)
TEST DETECTS
Pap smear of urinary epithelial cells Viral inclusions
Electron microscopy Virions
Immunofluorescence and
immunoperoxidase staining
Viral antigens
DNA probe analysis Viral nucleic acids
Nucleic acid hybridization in clinical
specimens
BK and JC viruses
Nucleic acids
Cell culture
Human diploid lung fibroblasts
Primary human fetal glial cells
Virus isolation-BK
Virus isolation-JC
Pap smear of urinary epithelial cells Viral inclusions
68. Diagnosis
• Serum or urine PCR
• Urine cytology
• Biopsy
• Electron microscopy of biopsy or urine
• Screening by urine cytology or PCR recommended
• Every three months for first 2 years post transplant
• With graft dysfunction
• With all biopsies
72. Diagnosis: In Situ Hybridization
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=eurekah&part=A74503
73. Diagnosis: Electron Microscopy
A) Free viral particles (~45 nm
diameter) shed in the urine.
B) Polyoma Allograft Nephropathy:
3D, cast-like polyomavirus
aggregates (‘Haufen’) in urine are
diagnostic of intra-renal disease.
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=eurekah&part=A74503
74. Treatment
• No known treatment
• However, it appears that some of fluoroquinolones may have therapeutic
potential.
Prevention
Non available
• Adjustment of Immunosuppression
• Cidofovir
• Leflunomide
75.
76. SV40
• SV40 replicates in the kidneys of monkeys without causing disease, but
can cause cancer in rodents under laboratory conditions.
• In the 1950s and early 1960s, well over 100 million people may have been
exposed to SV40 due to previously undetected SV40 contamination of
polio vaccine, prompting concern about the possibility that the virus might
cause disease in humans.
• Although it has been reported as present in some human cancers,
including brain tumors, bone tumors, mesotheliomas, and non-Hodgkin's
lymphomas, accurate detection is often confounded by high levels of
cross-reactivity for SV40 with widespread human polyomaviruses.
• Most virologists dismiss SV40 as a cause for human cancers
77. Species Virus name Abbreviation
Human polyomavirus 5 Merkel cell polyomavirus MCPyV
Human polyomavirus 8
Trichodysplasia spinulosa
polyomavirus
TSPyV
Human polyomavirus 9 Human polyomavirus 9 HPyV9
Human polyomavirus 12 Human polyomavirus 12 HPyV12
Human polyomavirus 13 New Jersey polyomavirus NJPyV
Human polyomavirus 1 BK polyomavirus BKPyV
Human polyomavirus 2 JC polyomavirus JCPyV
Human polyomavirus 3 KI polyomavirus KIPyV
Human polyomavirus 4 WU polyomavirus WUPyV
Human polyomavirus 6 Human polyomavirus 6 HPyV6
Human polyomavirus 7 Human polyomavirus 7 HPyV7
Human polyomavirus 10 MW polyomavirus MWPyV
Human polyomavirus 11 STL polyomavirus STLPyV
Human polyomavirus 14 Lyon IARC polyomavirus LIPyV