At least 15-20% of human tumors are caused by viruses that disrupt cellular signaling pathways related to cell growth and immune response. Various types of oncogenic viruses, particularly DNA and RNA viruses, play significant roles in cancer development, with complex mechanisms leading to persistent infections and malignancies. Notable examples include human papillomaviruses linked to cervical cancer and hepatitis viruses associated with liver cancer.

1. Human Cancer Viruses
Helen Kalandarishvili
UG 2023

2. At least 15% to 20% of all human
tumors worldwide have a viral cause.
As obligatory intracellular parasites, viruses encode
proteins that reprogram host cellular signaling
pathways that control proliferation, differentiation,
cell death, genomic integrity, and recognition by the
immune system.
Viruses that are associated with cancers:
✓ human papillomaviruses,
✓ Epstein-Barr virus,
✓ Human herpesvirus 8,
✓ Hepatitis B virus, hepatitis C virus,
✓ Two human retroviruses
two of great significance worldwide →
cervical cancer and liver cancer.
Many virus cause tumors in animals
✓ as a consequence of natural infection
✓ after experimental inoculationes can cause.
General

3. Stages of cancer development

4. Tenets (doctrine) of Viral Carcinogenesis
1. Viruses can cause cancer in animals and humans
2. Tumor viruses frequently establish persistent infections in natural hosts.
3. Host factors are important determinants of virus-induced tumorigenesis.
4. Viruses are seldom complete carcinogens.
5. Virus infections are more common than virus-related tumor formation
6. Long latent periods usually elapse between initial virus infection and tumor appearance
7. Viral strains may differ in oncogenic potential.
8. Viruses may be either direct- or indirect-acting carcinogenic agents.
9. Oncogenic viruses modulate growth control pathways in cells.
10. Animal models may reveal mechanisms of viral carcinogenesis.
11. Viral markers are usually present in tumor cells.
12. One virus may be associated with more than one type of tumor.

5. Taxonomy of Tumor Viruses
DNA viruses:
✓ encode viral oncoproteins
Papovaviruses
hepadnaviruses
herpesviruses
Adenoviruses
poxviruses
RNA viruses:
✓ highly oncogenic (direct-
transforming)
✓ weakly oncogenic (slowly
transforming)
Retroviruses
flaviviruses

6. Human Viruses and Associated Malignancies
Papillomaviridae →
Human papillomaviruses
Genital tumors
Squamous cell carcinoma
Oropharyngeal carcinoma
Herpesviridae →
EB virus
Nasopharyngeal carcinoma
Burkitt's lymphoma
Hodgkin's disease
B cell lymphoma
Human herpesvirus 8 Kaposi's sarcoma
Hepadnaviridae → Hepatitis B virus Hepatocellular carcinoma
Retroviridae → HTL virus Adult T cell leukemia
Human immunodeficiency virus AIDS-related malignancies
Flaviviridae → Hepatitis C virus Hepatocellular carcinoma

7. Multistep Carcinogenesis
Carcinogenesis is a multistep process → multiple genetic changes must occur to convert a normal cell into a
malignant one.
Intermediate stages:
✓ "immortalization"
✓ "hyperplasia,"
✓ "preneoplastic”
Tumors usually develop slowly
over a long period of time.
Multistep process of cellular evolution involvs:
✓ cellular genetic instability
✓ repeated selection of rare cells with some selective growth advantage
✓ a tumor virus usually acts as a cofactor, providing only some of the steps
required to generate malignant cells

8. How do viruses transform cells?
Virus infection provide a “hit” towards the genesis of cancer:
✓ Act as a “mutagen”
✓ Other cofactors (genetic, immunological, or environmental) may be needed for development of cancer
✓ Cell transformation is accompanied by the persistence of all or part of the viral genome and continual
expression of a limited number of viral genes.
✓ Viral oncogenes are expressed that alter normal cellular gene expression and signal transduction pathways
Summary:
▪ RNA viruses activate oncogenes
▪ DNA viruses negate tumor suppressors

9. Normal Chicken Embryo
Fibroblasts
Transformed by RSV

10. Cell Susceptibility to Viral Infections
At the cellular level, host cells are either permissive or nonpermissive for replication of a given virus.
Permissive cells support viral growth and
production of progeny virus.
Nonpermissive cells may be transformed, they do not
support viral growth and progeny virus production.
RNA tumor viruses are not lethal for the cells in which they replicate.
Not all cells from the natural host species are susceptible to viral replication or
transformation or both.
Most tumor viruses exhibit marked tissue specificity that may reflect
✓ variable presence of surface receptors for the virus,
✓ virus ability to cause disseminated infections,
✓ intracellular factors necessary for viral gene expression.

11. Retention of Tumor Virus Nucleic Acid
in a Host Cell
➢ The stable genetic change from a normal to a neoplastic cell generally requires the retention of viral genes in the cell.
➢ Integration of certain viral genes into the host cell genome.
✓ With DNA tumor viruses, a portion of the viral DNA may become integrated into the host cell chromosome or
maintained as episomal copies of the viral genome
✓ With retroviruses, the proviral DNA copy of the viral RNA is integrated in the host cell DNA.
➢ Virus-transformed cells may release growth factors that affect the phenotype of neighboring uninfected cells, thereby
contributing to tumor formation.
➢ Viral genes that drove tumor initiation may become unnecessary during tumor growth and may be lost from some
cells

12. Mechanisms of virus action
➢ Tumor viruses mediate changes in cell behavior by means of a limited amount of genetic information.
➢ Two general patterns:
✓ tumor virus introduces a new "transforming gene" into the cell (direct-acting),
✓ virus alters the expression of a preexisting cellular gene or genes (indirect-acting).
➢ The cell loses control of normal regulation of growth processes.
✓ DNA repair pathways are frequently affected, leading to genetic instability and a mutagenic phenotype
➢ Indirect-acting tumor viruses are not able to transform cells in culture .

13. Interactions of Tumor Viruses with Their Hosts
Persistent Infections
➢ Tumor viruses establish long-term persistent infections in humans.
➢ Levels of virus replication and tissue tropisms may vary among individuals (differences in genetic susceptibilities and
host immune responses).
➢ Very few cells in the host may be infected but the chronicity of infection presents the long-term opportunity for
survival of cells with virus-modified growth control mechanisms
Host responce
➢ Viruses must avoid detection, recognition and elimination by the host immune system to establish persistent
infections.
➢ Different viral evasion strategies have been identified:
✓ restricted expression of viral genes that makes infected cells nearly invisible to the host (Epstein-Barr virus in B
cells);
✓ infection of sites relatively inaccessible to immune responses (human papillomavirus in the epidermis);
✓ mutation of viral antigens that allows escape from antibody and T cell recognition (human immunodeficiency
virus);
✓ modulation of host major histocompatibility complex class I molecules in infected cells (adenovirus,
cytomegalovirus);
✓ inhibition of antigen processing (Epstein-Barr virus);
✓ infection and suppression of essential immune cells (human immunodeficiency virus).

14. Retroviruses
➢ Retroviruses contain an RNA genome and an RNA-directed DNA
polymerase (reverse transcriptase).
➢ RNA tumor viruses mainly cause tumors of the reticuloendothelial
and hematopoetic systems (leukemias, lymphomas) or of connective
tissue (sarcomas).
➢ Retrovirus genome consists of two identical subunits of single-
stranded, positive-sense RNA, each 7–11 kb in size.
✓ reverse transcriptase contained in virus particles is essential for
viral replication

15. Retroviruses
➢ Retrovirus particles contain:
✓ helical ribonucleoprotein within an icosahedral capsid
✓ outer membrane (envelope) containing glycoprotein
and lipid.
➢ Type-specific or subgroup-specific antigens are associated
with the glycoproteins in the viral envelope, which are
encoded by the env gene;
➢ Group-specific antigens are associated with the virion core,
which are encoded by the gag gene.
Structure

16. Retroviruses Structure
➢ The viral RNA is composed of three regions.
➢ At each end are repeats (called terminal repeats).
✓ The repeat sequences do not code for
proteins.
➢ In between the two repeats, there is a unique (not
repeated) region that contains the viral genes that
code for the proteins
✓ GAG
✓ POL
✓ ENV

17. Retroviruses Structure

18. Retroviruses Replication
The POL (Polymerase) gene products are:
➢ Reverse transcriptase (copies RNA to DNA) About 10 copies are present within the mature virus
➢ Integrase (integrates the viral genome into the host genome)
➢ RNase H (cleaves the RNA as the DNA is transcribed so that reverse transcriptase can make the second
complementary strand of DNA)
➢ Protease (cleaves the polyproteins).
✓ This virally encoded protease is the target of a new generation of antiviral drugs.

19. ➢ RNA viruses binding to a specific cell surface receptor, were uptake by endocytosis or by direct fusion to
the plasma membrane.
➢ The viral reverse transcriptase enzyme produces a DNA copy of the genome RNA within the capsid in the
cytoplasm.
✓ RNA (plus sense) is copied by reverse transcriptase to minus sense DNA.
✓ Reverse transcriptase acts as a DNA-dependent DNA polymerase and copies the new DNA into a
double strand DNA.
➢ The DNA enters the nucleus and is integrated random into cell DNA, forming the provirus.
✓ The newly formed viral DNA integrated into the host cell DNA using a virally encoded integrase
enzyme.
Replication
Retroviruses

20. Retroviruses
Replication
➢ The integrated provirus serves as template for the synthesis of viral transcripts, some of which are unspliced and
will be encapsidated as genomic RNAs and others, some of which are spliced, will serve as mRNAs.
✓ The proviral DNA is transcribed into viral RNA by the host enzyme, RNA polymerase II.
➢ Viral proteins are synthesized; the proteins and genome RNAs assemble; and particles bud from the cell.
➢ A salient feature of retroviruses is that they are not cytolytic - they do not kill the cells in which they replicate.

22. morphological types
Retroviruses
Type A particles occur only intracellularly and
appear to be noninfectious. Intracytoplasmic
type A particles, 75 nm in diameter, are
precursors of extracellular type B viruses.
Type B viruses - 100–130 nm in diameter and contain
an eccentric nucleoid. The prototype of this group is the
mouse mammary tumor virus, which occurs in "high
mammary cancer" strains of inbred mice
Type C viruses - the largest group of retroviruses. The
particles are 90–110 nm in diameter, and the electron-
dense nucleoids are centrally located. The type C
viruses may exist as exogenous or endogenous entities.
The lentiviruses are also type C viruses.
Type D viruses - poorly characterized. The particles
of 100–120 nm in diameter, contain an eccentric
nucleoid, and exhibit surface spikes shorter than
those on type B particles a

23. morphological types
Retroviruses

24. Retroviruses Classification
Retroviridae family is divided into 7 genera:
Alpharetrovirus avian leukosis and sarcoma viruses)
Betaretrovirus mouse mammary tumor virus
Gammaretrovirus mammalian leukemia and sarcoma
viruses
Deltaretrovirus human T-lymphotropic viruses and
bovine leukemia virus
Epsilonretrovirus fish viruses
Spumavirus viruses able to cause "foamy"
degeneration of inoculated cells
Lentivirus related to chronic infections with
slowly progressive neurologic
impairment, including the HIV

25. Retroviruses
Origin of retroviruses
➢ Retroviruses have been isolated from all vertebrate species.
➢ Most viruses are isolated from a single species, though natural infections across species barriers may occur.
➢ Group-specific antigenic determinants on the major internal (core) protein are shared by viruses from the same
host species.
➢ All mammalian viruses are more closely related to one another than to those from avian species.
➢ The RNA tumor viruses most widely studied experimentally are the sarcoma viruses of chickens and mice and the
leukemia viruses of mice, cats, chickens, and humans.

26. Retroviruses Origin of retroviruses
➢ They are spread horizontally and behave as
typical infectious agents.
➢ They initiate infection and transformation
only after contact.
➢ Gene sequences of exogenous viruses are
found only in infected cells.
➢ The pathogenic retroviruses all appear to
be exogenous viruses.
Exogenous Endogenous
➢ Genes are found in all cells of all vertebrates.
➢ They are usually not pathogenic for their host
animals.
➢ Do not produce any disease and cannot transform
cells in culture
➢ Viral genomes are transmitted genetically from
parent to offspring
➢ Virus may be induced to replicate either
spontaneously or by treatment with extrinsic
(chemical) factors.

27. Retroviruses Host Range of Retroviruses
Xenotropic viruses can replicate in some heterologous
(foreign) cells but not in cells of the natural host. Many
endogenous viruses have xenotropic host ranges
Host range of retroviruses depends on presence or absence of an appropriate cell surface receptor
Infection is initiated by an interaction between the viral envelope glycoprotein and a cell surface receptor.
Ecotropic viruses infect and replicate
only in cells from animals of the
original host species.
Amphotropic viruses exhibit a broad host range (able to
infect cells not only of the natural host but of
heterologous species as well) because they recognize a
receptor that is widely distributed.

28. Retroviruses
➢ Retroviruses have a simple genetic content, but there is some variation in the number and type of genes
contained.
➢ Genetic makeup of a virus influences its biologic properties
➢ The standard leukemia viruses (Alpharetrovirus and Gammaretrovirus) contain genes required for viral
replication:
✓ gag, which encodes the core proteins (group-specific antigens);
✓ pro, which encodes a protease enzyme;
✓ pol, which encodes the reverse transcriptase enzyme (polymerase);
✓ env, which encodes the glycoproteins that form projections on the envelope of the particle.
✓ The gene order in all retroviruses is 5'-gag-pro-pol-env-3'.
Genetic Content of retroviruses

29. Retroviruses

30. Retroviruses Human T-lymphotropic (HTLV) virus
➢The human T-lymphotropic virus was the first oncogenic human
retrovirus to be discovered.
➢It was first studied in 1977.
➢They have a marked affinity for mature T cells → Infects primarily
CD4+ T cells.
➢HTLV-1 and HTLV-2 share about 65% sequence homology and
display significant serologic cross-reactivity.
➢HTLV (human T-cell lymphotropic virus) causes:
✓Adult T-cell Leukemia/Lymphoma (Sezary T-cell Leukemia).
✓HTLV-associated myelopathy/tropical spastic paraparesis -
Nervous system degenerative disorder.
➢Both ALT and HAM are relatively rare diseases.

31. Retroviruses Human T-lymphotropic (HTLV) virus
➢ The virus is distributed worldwide, with an estimated 10 to 20
million infected individuals
➢ Clusters of HTLV-associated disease are found in certain
geographic areas:
✓Southern Japan, Melanesia, The Caribbean, Central and
South America, parts of Africa
➢Fewer than 1% of people worldwide have HTLV-1 antibody.
➢More than 10% of the population in endemic areas are
seropositive, and antibody may be found in 50% of relatives of
virus-positive leukemia patients.

32. Retroviruses Human T-lymphotropic (HTLV) virus
➢ Transmission of HTLV-1
✓ Mother-to-child via breast feeding
▪ Efficiency of transmission is 15– 25%.
✓ Blood transfusion
✓ Sexual (60% male to female versus 1% female to male transmission)
➢ The 5-year survival rate for patients with this cancer is < 5%.
➢ The cancer is thought to be due to the pro-oncogenic effect of viral RNA incorporated
into host lymphocyte DNA. .
➢ The lymphoma ranges from a very indolent and slowly progressive type to a very
aggressive and nearly uniformly lethal proliferative type

33. Retroviruses Adult T-cell Leukemia
➢ These features are caused by proliferating T cells infiltrating these
organs.
➢ In the blood, the malignant T cells have a distinct “flower-shaped”
nucleus.
➢ Hypercalcemia due to increased osteoclast activity within the bone
lesions is seen.
➢ Patients with ATL often have reduced cell-mediated immunity, and
opportunistic infections with fungi and viruses are common
ATL (Adult T-cell Leukemia) is characterized by lymphadenopathy, hepatosplenomegaly, lytic bone lesions, and
skin lesions.

34. Retroviruses
HTLV-associated myelopathy/tropical spastic paraparesis
✓ Only 0.3 to 4% of infected individuals develop HAM/TSP
✓ Motor and sensory changes in the extremities
✓ Spastic gait in combination with weakness of the lower limbs
✓ Bladder dysfunction (neurogenic bladder) and bladder cancer
✓ Mild cognitive impairment
✓ Erectile dysfunction
➢ Progression of symptoms occurs slowly over a period of years.
➢ HAM occurs primarily in women of middle age.

35. Retroviruses
➢ Screening donated blood for the presence of
antibodies
➢ Using condoms to prevent sexual transmission
➢ Encouraging women with HTLV antibodies to refrain
from breastfeeding.
DIAGNOSIS
TREATMENT PREVENTION
➢ Detection of antibodies in the patient’s serum using the ELISA
➢ PCR
➢ Isolation of HTLV in cell culture is not done.
✓ ATL is diagnosed by finding malignant T cells in the lesions.
✓ HAM is diagnosed by the presence of HTLV antibody in the spinal
fluid or finding HTLV nucleic acids in cells in the spinal fluid
➢ There is no specific antiviral treatment for
HTLV infection
➢ There is no vaccine against HTLV.
➢ ATL is treated with anticancer
chemotherapy regimens.

36. DNA TUMOR VIRUSES
Fundamental differences exist between the oncogenes of DNA and RNA tumor viruses.
✓ The transforming genes carried by DNA tumor viruses encode functions required for viral replication
and do not have normal homologs in cells.
✓ The DNA virus transforming proteins complex with normal cell proteins and alter their function.
✓ In contrast, RNA tumor viruses (retroviruses) either carry transduced cellular oncogenes that have no
role in viral replication or they act through indirect mechanisms.

37. PAPILLOMA VIRUSES
➢ Double stranded DNA
➢ Non enveloped virus
➢ Icosahedral nucleocapsid
➢ Spread by:
✓ skin-to-skin contact
✓ sexual contact
✓ or from mother to baby.
➢ HPV infects squamous epithelial cells and induce cytoplasmic vacuoles.
✓ These cells are called koilocytes

38. PAPILLOMA VIRUSES

39. PAPILLOMA VIRUSES
➢ Life cycle of HPV starts with the infection of the host cell.
➢ The virus DNA is released within the nucleus
➢ Numerous cellular transcription factors interact with the non-coding viral regulatory region (LCR), starting
transcription of the two HPV transforming early genes (E6 and E7) - implicated in carcinogenesis.
➢ They encode proteins that inactivate proteins encoded by tumor suppressor genes in human cells (the p53 gene
and the retinoblastoma [RB] gene, respectively).
➢ Inactivation of the p53 and RB proteins is an important step in the process by which a normal cell becomes a
cancer cell.
Life cycle

40. PAPILLOMA VIRUSES

41. PAPILLOMA VIRUSES
➢ The peak incidence of HPV infections occurs in adolescents and young adults under 25
years of age.
➢ HPV is the virus that causes warts.
➢ Spread by sexual contact or from mother to baby.
➢ Genital warts appear 6 weeks to 8 months after contact with an HPV infected person.
➢ There is widespread diversity among papillomaviruses.
➢ In 1976 was published the hypothesis that human papilloma virus plays an
important role in the cause of cervical cancer.
➢ More than 100 distinct human papillomavirus (HPV) types have been recovered,
but, not all are associated with cancers.
➢ In 1983 and 1984 was identified HPV16 and HPV18 in cervical cancer.

42. PAPILLOMA VIRUSES
Mechanism of infection
➢ All PV exhibit extreme specificity for infection on epithelial cells.
➢ Papillomavirus epitheliotrophy determined by the interaction of specific transmission
factors with the viral regulatory region LCR.
➢ The infection normally results in hyperproliferation of the host cell and may lead to
transformation and immortalization.

43. PAPILLOMA VIRUSES
How HPV causes Cancer
➢ HPV DNA integrates into the host genome.
➢ The proteins E6 and E7 are produced from the resultant DNA.
➢ E6 binds and degrades p53 (a tumor suppressor gene).
➢ If the DNA is altered, the cell keeps replicating. The mutation rate of the cell increases.
➢ E7 binds and degrades retinoblastoma gene (another tumor suppressor gene).
➢ Retinoblastoma normally keeps the cell from growing too fast or responding to growth stimulators. This
inhibitory factor is now lost.
➢ Without these two mechanisms to slow down cell growth and prevent mutation. . .
➢ Malignant Transformation Occurs.

44. PAPILLOMA VIRUSES
Life Cycle

45. PAPILLOMA VIRUSES
➢ There are at least 100 different types of HPV, many of which cause distinct clinical entities.
➢ 30 HPV types primarily infect the squamous epithelium of the lower anogenital tracts of both males and females.
➢ HPV types 6, 11, 42, 43, or 44 present as papillary condylomas, may also present as flat lesions that may or may not
be visible to the unaided eye are part of the “low-risk” HPV types.
➢ Types 16, 18, 31, 33, 35, 45, 51, 52, 56 - “high-risk” types in relation with cervical and other lower genital tract
cancers.
✓ HPV types 16 and 18 are considered to be the higher cancer risk
➢ No in vitro infectivity assay
✓ papillomavirus isolates are classified using molecular criteria.
✓ Virus "types" are at least 10% dissimilar in the sequence of their L1 genes.
HPV Types

46. PAPILLOMA VIRUSES
Common wart Flat wart Plantar warts

47. PAPILLOMA VIRUSES
➢ Cervical cancer is the second most frequent cancer in women worldwide
(about 500,000 new cases annually) and is a major cause of cancer deaths in
developing countries.
✓ HPV-16 or HPV-18 is found most frequently in cervical carcinomas,
responsible for 70% of all cervical cancers.
➢HPV genital infections are sexually transmitted and represent the most
common sexually transmitted disease.
➢Cancer occurs in people having been infected with HPV for a long time,
usually over a decade or more (persistent infection)
➢Anal cancer is associated with high-risk HPV infection.

48. PAPILLOMA VIRUSES
➢The role of men as carriers of HPV as well as vectors for transmission of
infections is well documented.
➢However, most penile HPV infections in men are subclinical and do not
result in HPV-associated disease.
➢Oropharyngeal cancers are also linked to HPV infections, especially by
type 16.
➢Immunosuppressed patients experience an increased incidence of warts
and cancer of the cervix.

49. PAPILLOMA VIRUSES
➢ Genital warts - sometimes called condylomata acuminata.
✓ soft, moist or flesh colored, and appear in the genital area within weeks or months after infection.→ HPV
types 6 and 11.
✓ Sometimes appear in clusters and are either raised or flat, small or large.
✓ Most common in childhood.
✓ Common warts are usually found on the hands and feet, elbows or knees → HPV-1, HPV 4
➢ Women: appear in the vulva, cervix, vagina and anus;
➢ Men- can appear on the scrotum or penis.
➢ The role of men as carriers of HPV as well as vectors for transmission of infections is well documented

50. PAPILLOMA VIRUSES
➢ Laryngeal papillomas in children- also called recurrent respiratory papillomatosis
✓ caused by HPV-6 and HPV-11, the same viruses that cause benign genital condylomas.
✓ infection is acquired during passage through the birth canal of a mother with genital warts.
➢ While laryngeal papillomas are rare, the growths may obstruct the larynx and must be removed repeatedly by
surgical means.
➢ About 3000 cases of this disease are diagnosed annually; up to 3% of children may die.

51. PAPILLOMA VIRUSES
Diagnosis
• A wart can be confirmed microscopically on the basis of its characteristic
histologic appearance.
✓ Warts are removed - surgical cryotherapy, or chemical means (10% to 25%
solution of podophyllin, Liquid nitrogen, salicylic acid ).
• Papillomavirus infection can be detected:
✓ Pap smears (Pap test) - the presence of koilocytotic (vacuolated
cytoplasm) squamous epithelial cells, which are rounded and occur in
clumps.
✓ DNA molecular probe and polymerase chain reaction (PCR) analysis of
cervical swabs and tissue specimens
✓ Papillomaviruses do not grow in cell cultures.

52. PAPILLOMA VIRUSES
Treatment
Genital warts can be treated by a doctor and by different methods.
Podofilox gel: A patient-applied treatment for external genital warts.
Imiquimod cream: A patient-applied treatment.
Chemical treatments
(including trichloracetic acid and podophyllin)
which must be applied by a trained health care provider to
destroy warts.
Cryotherapy: Uses liquid nitrogen to freeze off the warts.
Laser therapy: Uses a laser beam or intense lights to destroy the warts.
Electrosurgery: Uses and electric current to burn off the warts.
Surgery: Can cut away the wart in one office visit .
Interferon: an antiviral drug, which can be injected directly into warts.

53. PAPILLOMA VIRUSES
Vaccine
➢There are two vaccines against HPV:
➢ Gardasil - a recombinant vaccine against four types of HPV, contains the capsid proteins
➢ types 6 and 11 - genital warts
➢ types 16 and 18 - cervical, penile, and anal carcinoma.
➢A quadrivalent HPV vaccine was approved in the United States in 2006.
➢ Cervarix - a recombinant vaccine contains the proteins only of types 16 and 18.
➢Recommended for routine vaccination at age 11 or 12 years.
➢Vaccination is not recommended for everyone older than age 26 years.
➢HPV vaccine works best when given before any exposure to HPV.
➢It is not effective against established HPV disease.

54. POLYOMA VIRUSES
➢ Polyomaviridae family - natural hosts are primarily mammals and birds
➢ Human polyoma viruses - BK and JC were discovered in 1971.
➢ Small viruses (diameter 45 nm)
➢ Circular genome of double-stranded DNA
➢ Non Enveloped capsid exhibiting icosahedral symmetry
➢Both viruses may persist in the kidneys and lymphoid tissues of healthy individuals after primary infection and
may reactivate when the host’s immune response is impaired
➢They often persist as latent infections, but may produce tumors in a host of a different species

55. POLYOMA VIRUSES

56. POLYOMA VIRUSES
➢ JC virus causes progressive multifocal leukoencephalopathy.
➢ Virus infects and kills oligodendroglia, causing demyelination of the nerve cells in the white matter of the
brain.
➢ Neurons are unaffected. It is not an encephalitis because there is no inflammation in the brain.
➢Antibodies are found in approximately 75% of normal human sera, indicating that infection is widespread.
➢The clinical picture → visual field defects, mental status changes, and weakness.
➢The disease rapidly progresses to blindness, dementia, and coma, and most patients die within 6 months.
➢The diagnosis - PCR
➢There is no effective antiviral treatment, but cidofovir may be beneficial.
JC Virus

57. POLYOMA VIRUSES
➢ BK virus is widely distributed in human populations, as evidenced by the presence of specific antibody in 70–
80% of adult sera.
➢ It is the cause of polyomavirus-associated nephropathy in renal transplant recipients
✓ a serious disease that occurs in up to 5% of recipients
✓ results in graft failure in up to 50% of those affected patients.
➢ Infection usually occurs during early childhood and is not associated with any disease at that time.
➢ Asymptomatic shedding of BK virus in the urine of immunocompromised patients and pregnant women
occurs in the third trimester
➢ There is no antiviral therapy effective against BK virus.
➢ Recently, BK viral DNA has been associated with human prostate cancer
BK Virus

58. POLYOMA VIRUSES
➢ Three other human polyoma viruses have recently been described: KI, WU and Merkel cell
polyomavirus.
➢ Merkel cell virus causes a rare skin cancer (Merkel cell carcinoma).
➢ Human polyomavirus can cause cancer in humans and is most commonly associated with
✓ Rectal polyps
✓ Breast cancer
✓ Prostate cancer
✓ Anogenital cancers
✓ Mesotheliomas

59. POLYOMA VIRUSES
➢The diagnosis of polyomavirus almost always occurs after the
primary infection as it is either asymptomatic or subclinical.
➢Antibody assays are commonly used to detect presence of
antibodies against individual viruses.
➢The organs to which each human polyomavirus has tropism
and causes disease.

60. Herpesviruses
➢ Large viruses with icosahedral symemtry (diameter 125–200 nm) and a linear genome of double-
stranded DNA (125–240 kbp)
✓ Typically cause acute infections followed by latency and recurrence in the host
➢ In humans, herpesviruses have been linked to several specific types of tumors.
➢ Kaposi's sarcoma-associated herpesvirus, also known as human herpesvirus 8 (KSHV/HHV8), is not as
ubiquitous as most other human herpesviruses.
➢ Herpesvirus 8 (KSHV/HHV8) is suspected of being the cause of Kaposi's sarcoma, primary effusion
lymphoma, and a particular lymphoproliferative disorder.
➢ KSHV has a number of genes that may stimulate cellular proliferation and modify host defense
mechanisms
➢ Transmitted both sexually and by saliva

61. Epstein-Barr (EB) herpesvirus
➢ EBV herpesvirus causes acute infectious mononucleosis when it infects B lymphocytes of susceptible humans.
➢ Normal human lymphocytes have a limited life span in vitro, but EB virus can immortalize such lymphocytes into
lymphoblast cell lines
➢ EB virus is etiologically linked to Burkitt's lymphoma - a tumor most commonly found in children in central Africa;
➢ Nasopharyngeal carcinoma (NPC), more common in some Chinese populations and Alaskan Eskimos than other
populations;
✓ Consumption of salted or dried fish may be a dietary cofactor
➢ Posttransplant lymphomas; Hodgkin's disease.
✓ These tumors usually contain EB viral DNA (both integrated and episomal forms) and viral antigens.
✓ Malaria may be a cofactor of African Burkitt's lymphoma
➢ EB virus encodes a viral oncogene protein (LMP1) - able to transform rodent fibroblasts and is essential for
transformation of B lymphocytes
➢ EB virus is very successful at avoiding immune elimination;
➢ Possibly due to the function of EBNA1 to allow infected cells to escape killing by cytotoxic T lymphocytes.

62. END of Cancer Viruses!