human_papilomma_viruses. definition, species and category. the virus has the great health effect on men and women; specially its effect on the reproductive organs. An infection that causes warts in various parts of the body, depending on the strain. Human papillomavirus (HPV) is the most common sexually transmitted infection (STI). Many people with HPV don't develop any symptoms but can still infect others through sexual contact. Symptoms may include warts on the genitals or surrounding skin. There's no cure for the virus and warts may go away on their own. Treatment focuses on removing the warts. A vaccine that prevents the HPV strains most likely to cause genital warts and cervical cancer is recommended for boys and girls. HPV infection is a viral infection that commonly causes skin or mucous membrane growths (warts). There are more than 100 varieties of human papillomavirus (HPV). Some types of human papillomavirus (HPV) infection cause warts, and some can cause different types of cancer. Most HPV infections don't lead to cancer. But some types of genital HPV can cause cancer of the lower part of the uterus that connects to the vagina (cervix). Other types of cancers, including cancers of the anus, penis, vagina, vulva and back of the throat (oropharyngeal), have been linked to HPV infection. These infections are often transmitted sexually or through other skin-to-skin contact. Vaccines can help protect against the strains of HPV most likely to cause genital warts or cervical cancer. Cervical cancer Nearly all cervical cancers are caused by HPV infections, but cervical cancer may take 20 years or longer to develop after an HPV infection. The HPV infection and early cervical cancer typically don't cause noticeable symptoms. Getting vaccinated against HPV infection is your best protection from cervical cancer.

1. Human Papillomaviruses (HPV)

2. Objectives
• Explain the properties of papillomavirus
• Describe the pathogenesis and clinical features Papillomavirus
infection
• Illustrate epidemiology papilomavirus
• Describe the diagnosis papilomavirus infection

3. HPV…
Properties
• Genome is circular dsDNA
• Non-enveloped with icosahedral symmetry
• Possess capsomeres surround the genome
• Major & minor capsid protein comprises outer protein coat of
the virus
• More than 80 types of HPV

4. • Three major regions comprise the HPV genome :
▪ Early region (E1-8) consists of genes responsible for
transcription, plasmid replication, & cellular transformation
▪ The late region codes for the major (L1) and mnor (L2) capsid
proteins &
▪ Control region contain the regulatory elements for
transcription and replication
• Replication is in host cell nucleus
• Undergo cell transformation

5. HPV Gene Coding Regions

6. HPV gene products & their function
genes Functions
E1 Initiation of DNA replication
E2 Transcriptional regulation/DNA replication
E3 ??????
E4 Disrupts cytoskeleton
E5 Transforming protein, interacts with growth factors receptors
E6 Transforming protein, binds to p53 gene, leading to degradation
E7 Transforming protein, binds to pRB
E8 ???????
L1 Major capsid protein
L2 Minor capsid protein

7. Fig. Differentiation of normal cutaneous squamous epithelium &
papillomaviral activities in productively infected benign lesions. The various
epithelial strata & the host-differentiation, stage-specific, gene-expression
profile are indicated in the left and center panels. Source: Virology, 4th ed,
Knipe & Howley, eds, Lippincott Williams & Wilkins, 2001.
Papillo mavirus replication & differentiation of the epidermis

8. Fig. Replication cycle of a papillomavirus. To establish a wart or papilloma, the virus must infect a
basal epithelial cell. Initial steps in the replication cycle include : attachment (1), uptake (2),
endocytosis (3), and transport to the nucleus and uncoating of the viral DNA (4). Early-region
transcription (5), translation of the early proteins (6), viral DNA replication (7), vegetative viral DNA
replication (8), transcription of the late region (9), production of the capsid proteins L1 and L2 (10),
assembly of the virion particles (11), nuclear breakdown (12), and release of virus (13). (From Fields
Virology, 4th ed, Knipe & Howley, eds, Lippincott Williams & Wilkins, 2001.
Papillo mavirus replication

9. Fig. Medical Microbiology, 5th ed., Murray, Rosenthal & Pfaller,
Mosby Inc., 2005..
Papillomavirus pathogenesis

11. Immune Response to HPV Infection
• A cell-mediated immune response plays an important role in
controlling the progression of natural HPV infection.
• Histologic examination of lesions in individuals who
experience regression of genital warts demonstrates
infiltration of T cells and macrophages.
• CD4+ T cell regulation is particularly important in controlling
HPV infections, as evidenced by the higher rates of infection
and disease among immunosuppressed individuals,
particularly those who are infected with HIV.

12. • Specific T-cell responses may be measured against HPV
proteins, the most important of which appear to be the E2
and E6 proteins.
• In women with HPV-16 cervical infection, a strong T-cell
response to HPV-16-derived E2 protein is associated with a
lack of progression of cervical disease.

13. Epidemiology
• HPV prevalence and diseases are type specific
• There is regional & ethnic variation in HPV types
• HPV 16,18,33 and 45 are mostly found in cervical cancers
worldwide in order of prevalence
• HPV 16 & 18 present in 50% & 20% of all cases respectively
• HPV 16 and HPV 18 are predominant types in newborns

14. • Types 6 and 11 are commonly associate with genital warts
(Condyloma acuminatum)
• Types 2,4,29 & 57 occur in common skin warts
• No complete data on HPV prevalence in developing
countries

15. Clinical genital tract and mucosal HPV’s
(From Fields Virology, 4th ed, Knipe & Howley, eds, Lippincott
Williams & Wilkins, 2001.)

18. Transmission
1. Sexual contact
• HPV is transmitted by sexual intercourse, by oral sex, and possibly by
touching of a partner’s genitalia.
• Grater than 95% of infection is through sexual contact
• In children associated with sexual abuse
2.Vertical transmission
▪ Less frequent mode of transmission
▪ Difficult to detect due to the latency period between the infant’s
exposure at birth & symptom presentation
3. Other pathways
• Non-sexual transmission, e.g. contact with infected urogenital
secretions or bathing together

19. Risk factors for HPV
1. Sexual behavior
• Is a primary risk factor for infection
• Women with multiple sex partners have a higher risk than
monogamous women
2. Immune suppression
• Is a risk factor for all people exposed to HPV
• A person with a pre-existing immuno-compromised state
and/or concurrent genital infection has a 17-fold increased risk
of developing the diseases

20. ▪ Increased risk of HPV in people with HIV infection E.g: A study
of 207 HIV-exposed women in New York showed that HPV
prevalence was 23% among HIV seronegatives & 46% among
HIV seropositives.
▪ The HIV+ women also had higher rates of oncogenic HPV
types, which progressed to cancer (as well as other HPV
types).

21. 3. Age
• Young women, between the ages of 15 and 25 have a two fold
higher risk of developing an HPV infection than women over 35
4. Other possible risk factors
Pregnancy, smoking , concurrent herpes infections , others
►Associated with increased HPV infection in several studies, but
their significance is not conclusive

22. 5. Socioeconomic variables
Poverty, domestic violence, sexual abuse, inadequate
health Care & lack of information
►Can facilitate disease transmission , prevent early detection &
treatment

23. Effects of HIV on HPV-Associated Disease
• HIV infection accelerates the natural progression of HPV
infections.
• HIV-infected persons are more likely than other individuals to
develop genital warts and to have lesions that are more
recalcitrant to treatment.
• HIV infection has been consistently associated with
precancerous cervical lesions, including low-grade cervical
intraepithelial neoplasia (CIN) and CIN 3, the immediate
precursor to cervical cancer.
• Women with HIV/AIDS have significantly higher rates of
cervical cancer and of subsets of some vulvar, vaginal, and
oropharyngeal tumors than women in the general population.

24. • The incidence of anal cancer is also strongly influenced by HIV
infection.
• HIV-infected men who have sex with men (MSM) and HIV-
infected women have much higher rates of anal cancer than
HIV-uninfected populations.

25. Diagnosis
▪ Cytology (PAP smear; koilocytosis)
▪ Immunohistochemistry
▪ Nucleic acid
▪ Electron microscopy
Treatment/prevention
▪ Surgery, Early detection & treatment
▪ Follow up of pre-malignant lesions
▪ Recombinant subunit (VLP) vaccine

26. • The vaccines use virus-like particles (VLPs) that consist of the
HPV L1 major capsid protein.
• The L1 protein self-assembles into VLPs when expressed in
eukaryotic cells (i.e., yeast for the gardasil vaccine or insect
cells for the cervarix vaccine).
• These VLPs contain the same epitopes as the HPV virion.
However, they do not contain genetic material and cannot
transmit infection.
• The immunogenicity of HPV vaccines relies on the
development of conformational neutralizing antibodies to
epitopes displayed on viral capsids.

27. ▪ Bivalent Vaccine (Cervarix) A bivalent L1 VLP vaccine (HPV-16
and -18), marketed under the name Cervarix, is administered
by IM injection at months 0, 1, and 6.
▪ Quadrivalent Vaccine (Gardasil) A quadrivalent L1 VLP (HPV-
6, -11, -16, and -18) vaccine, marketed under the name
Gardasil, is administered IM at months 0, 2, and 6.

28. Summary
• Structure
Small (8 kb) circular dsDNA genome, naked capsid
• Pathogenesis
▪ Transmission by direct contact or sexual; skin, mucosa
▪ Replication in nucleus of basal cells of epithelium; very host
dependent; coupled to epithelial differentiation
▪ Primarily cellular immune response
▪ Transforming infection; warts are tumors; cervical
carcinoma

29. References
• Medical Microbiology, 5th ed., Murray, Rosenthal &
Pfaller, Mosby Inc., 2005
• Basic Virology. Edward K.Wagner,3rd ed.,2006
• Medical Microbiology, Jawtz,Melnick, & Adelberg’s,24th
Edition, vishal
• Medical Microbiology,An Introduction to Infectious
Disease,Sherris,4th Edition,2004

30. • Adenoviruses
– Naked viruses with an icosahedral nucleocapsid containing a
double-stranded DNA genome
– One of the Causative agents of the common cold
– Over 50 serotypes - human source
– Replicate well only in epithelial cells
⮚ Transmission
⮚air droplets
⮚by contact contaminated fomites
⮚Faecal–oral route
⮚The incubation period - 5 to 10 days 30

31. • Syndromes associated with Adenovirus
– Pharyngitis
– Pneumonia
– Acute respiratory diseases
– Pharyngo conjunctival fever (conjunctivitis)
– Enteric infections (diarrhoea & vomiting)
– Urinary tract infections
31

32. 1. Pharyngitis
– Type 1,3, 5 & 7 are responsible
– Major cause of non-bacterial Pharyngitis and tonsillitis
2. Pneumonia
– Types 3 and 7 - adults;
– Type 7 - cause serious and fatal pneumonia- infants and young children
3. Acute respiratory diseases (ARD)
1. Types 4,7 and 21
– Characterized by Pharyngitis, fever, cough & malaise
– Respiratory symptoms last for about 1 week
32