Oncovirus and Prions Group4

ONCOVIRUSES AND PRIONS
SANTOS, ARRION TOLENTINO, MELANIE VILLANUEVA, MICHAL

HEPATITIS B
• Hepatitis B virus is a partially dsDNA enveloped virus that belongs to the

Hepadnaviridae family. Hepatitis B surface antigen (HBsAg) is found on the surface
of the virus and circulates in the bloodstream as 22-nm particles.
• The total diameter of the virus is around 45 nm. Hepatitis B antigen (HBcAg) and a
central antigen (HBcAg) are also present in the virion (HBeAg). HBV has eight
genotypes (A to H), and some studies have shown a difference in clinical outcome
depending on the genotype.
• Its primary tissue tropism is the liver
• (Eliason, 1940)Eliason, N. E. (1940). A Textbook. In American Speech (Vol. 15, Issue 3). https://doi.org/10.2307/486972
HEPATITIS B
• Double stranded circular DNA, has 3200 bp in length

• It is known to establish chronic infection in infants and eventually serves a major
factor in development of liver disease and hepatocellular carciinoma.
• It has 2 major polypeptides, glycosylated, present in HBsAg, polypeptide, present in
HBcAg.
HEPATITIS B
PATHOGENECITY AND PATHOLOGY
• Transmission: Sexual, perinatal, and parenteral routes are the most common modes of transmission. The
most common routes of transmission in the United States are heterosexual and male homosexual sexual
intercourse.
• HBV reaches the body via the bloodstream and infects the hepatocytes in the liver. The HBV-infected
hepatocytes are then attacked by cytotoxic T cells.
• The incubation period for HBV infection ranges from 2 to 6 months.
• Symptoms such as fever, anorexia, and hepatic tenderness appearing gradually. Jaundice affects only
about 10% of children under the age of five, although it is much more frequent in older children and
adults (32 percent to 54 percent ).
• The virus is gradually removed from the bloodstream as the immune response is triggered, and most
patients become noninfectious.
HEPATITIS B
• The presence of HBsAg in a patient's
serum means that he or she is infected with
HBV, is a chronic carrier, or is in the
incubation phase. Early in the course of the
disease, IgM anti-HBc emerges, indicating
an acute infection. The presence of IgM
anti-HBc supports the diagnosis of acute
HBV infection in patients that do not have
HBsAg and have not yet developed anti-
HBs.
• (Eliason, 1940)Eliason, N. E. (1940). A Textbook. In American

Speech (Vol. 15, Issue 3). https://doi.org/10.2307/486972
HEPATITIS B
• Diagnostic Test:
• ELISA, is used for HBV antigens and antibodies.
• For viral DNA, polymerase chain reaction is used.
• Prevention and treatment:
• Vaccine
• Viral genotype usually includes antivirals and interferon
• Recombinant IFN- and pegylated IFN- are currently the only therapies that have been shown to be effective in the
treatment of patients that have been infected with HBV or HCV for a long time.
• Lamivudine is an antiviral drug that is used to treat chronic hepatitis infections.
• The cure for chronic hepatitis B end-stage liver damage is orthotopic liver transplantation.
• Jennings, C. Oncoviruses. https://www.vumc.org/chtn/sites/vumc.org.chtn/files/public_files/Oncoviruses!.ppt

HEPATITIS C
• HCV is a ssRNA virus belonging to the Hepacivirus genus in the Flaviviridae family.
• A main protein, two envelope glycoproteins, and several nonstructural proteins are
encoded by the genome, which is 9.4 kb in size.
• Positive stranded RNA virus
• Six genotypes and more than 100 subtypes
• Hepatitis C virus (HCV) has a very narrow species and tissue tropism
HEPATITIS C
• The HCV genome is a positive-sense RNA molecule of approximately 9500

nucleotides.
• There are highly conserved 5' and 3' untranslated regions flanking an approximately
9000 nucleotide single open reading frame which encodes a large polyprotein of about
3000 amino acids
HEPATITIS C
Transmission
• While infection can be transmitted via perinatal and sexual transmission, and
parenteral transmission has been identified as a major route of infection, HCV
antibody has been found in patients whose transmission routes are unknown or who
have no identifiable risk factors.
HEPATITIS C
PATHOGENESIS
• HCV is a non-cytopathic virus that enters the liver cell and replicates at the same time,
causing cell necrosis through a variety of mechanisms, including immune-mediated
cytolysis, as well as hepatic steatosis, oxidative stress, and insulin resistance.
Irshad, M., Mankotia, D. S., & Irshad, K. (2013). An insight into the diagnosis and pathogenesis of hepatitis C virus infection. World journal of
gastroenterology, 19(44), 7896–7909. https://doi.org/10.3748/wjg.v19.i44.7896
HEPATITIS C
Diagnostic Test
• Enzyme immunoassay
• Recombinant immunoblot assay
HEPATITIS C
TREATMENT
• Treatment for virus = interferon + ribavirin, other antivirals + ribavirin, liver

transplantation (treatment based on genotype)
• Treatment for HCC = liver resection/transplantation, TACE, adjuvant chemo, XRT

HUMAN T-LYMPHOTROPIC VIRUS (HTLV-1)
• The Oncovirinae subfamily includes the human T-lymphotropic viruses HTLV-1,

HTLV-2, and HTLV-5. While these viruses are not cytolytic, they have been linked to
a variety of leukemias, sarcomas, and lymphomas.
• HTLVs are enveloped viruses with a diameter of approximately 80–100 nm.
• The HTLV virions contain two covalently bound genomic RNA strands, which are
complexed with the viral enzymes reverse transcriptase, integrase and protease, and
the capsid proteins.
• The outer part of the virions consists of a membrane-associated matrix protein and a
lipid layer intersected by the envelope proteins
• HTLV-1 can infect different cell types (T cells, B cells, dendritic cells, fibroblasts,
etc.) in tissue culture. However, it can transform only T cells both in vitro and in vivo.
• HTLV-1 induces the clonal proliferation of T lymphocytes, mainly CD4-positive T
cells, and to a lesser extent, CD8-positive T cells
PATHOGENESIS
• Virus enters T-cell and copies the two strands of RNA into double-stranded DNA that
can incorporate into the host cell's genes (much like HIV)
• -It's thought to be sexually transmitted or passed on by breastfeeding.
DIAGNOSTIC TEST
• Typically, an EIA (enzyme immunoassay) test method is used initially to

detect HTLV-I and HTLV-II antibodies in the blood.
• If the initial test is positive, a second method, such as Western blot, is ordered to
confirm the finding and to help distinguish between HTLV-I and HTLV-II.

TREATMENT
• Prosultiamine, azacytidine, TDF (reverse-transcriptase inhibitor), and PCOANs are

used to treat the virus.
• -Cancer treatment: zidovudine + CHOP; ATL treatment involves purine analog chemo
and immunotherapy, splenectomy, and bone marrow transplant; HCL treatment
includes purine analog chemo and immunotherapy, splenectomy, and bone marrow
transplant.

HUMAN PAPILLOMAVIRUS (HPV)
• HPVs, which belong to the genus Papillomavirus in the family Papillomaviridae, cause
papillomas, or warts. Some HPV forms have been related to cancer, including cervical cancer,
despite their association with the common wart.
• There are over 100 different types of these small dsDNA viruses, with over 40 of them being
sexually transmitted and referred to as genital types. Both children and young adults are believed
to be infected with HPV 1, 2, 3, and 4, with no major consequences.
• Different HPV forms have different tissue tropism depending on whether the viruses preferentially
invade cutaneous or mucosal epithelial cells. Based on their association with genital tract cancers,
genital HPVs are further classified as medium, intermediate, or high risk.
• Papillomaviruses are small, non-enveloped, icosahedral DNA viruses that have a diameter of 52–
55 nm.
• The viral particles consist of a single double-stranded DNA molecule of about 8000 base-pairs
(bp) that is bound to cellular histones and contained in a protein capsid composed of 72
pentameric capsomers.
• Papillomaviruses are highly species and tissue restricted, and these viruses display both
mucosotropic, cutaneotropic or dual tropism for epithelial tissues
• It's spread by sexual intercourse and skin-to-skin contact; it's even spread (rarely)
during childbirth.
• Cancers and recurrent respiratory papillomatosis are caused by a variety of subtypes,
including types 16 and 18. (RRP)
• HPV types 6 and 11 are linked to genital warts. HPV is responsible for almost all
cervical cancers and all cases of genital warts.
PATHOGENESIS
• HPV infection occurs at the basal cell layer of stratified squamous epithelial cells.
• Infection stimulates cellular proliferation in the epithelium and infected cells display a broad
spectrum of changes, ranging from benign hyperplasia to dysplasia to invasive carcinoma.
• To effectively replicate, HPV must utilize the host cellular machinery.
• During the process, the viral protein product encoded by E6 binds to the p53 tumor
suppressor gene product, which results in the premature degradation of the p53 protein.
• The E7 protein binds to a tumor suppressor protein—the retinoblastoma protein—and
inhibits its function.
• These protein products mediate much of the virus’ oncogenic potential and their production
represents a key difference between the low- and high-risk strains of HPV.
DIAGNOSTIC TEST
• Cytology — the Papanicolaou test, commonly referred to as a Pap smear, is a useful

screening test to detect cervical cytologic abnormalities.
• High-Risk HPV Nucleic Acid Testing — A definitive diagnosis of HPV infection is
based on detection of viral nucleic acid (DNA or mRNA). Clinical HPV tests that
detect different high-risk types of HPV DNA in cells scraped from the cervix are
commercially available

TREATMENT
• Virus vaccination (Gardasil and Cervarix)

• Cautery or cryotherapy for warts/cancer
• Condoms are encouraged, as is circumcision.

KAPOSI SARCOMA HHV-8
• Human herpesvirus 8, a member of the Rhadinovirus family, has been found in all
types of Kaposi sarcoma, including AIDS-related, Mediterranean, HIV-1–negative
endemic to Africa, and post-transplantation.
• It's also been linked to the progression of primary effusion lymphomas and
multicentric Castleman disease.
• The majority of herpes genes contain upstream promoter and regulatory sequences, an
initiation site followed by a 5' nontranslated leader sequence, the open reading frame
(Orf) itself, some 3' nontranslated sequences, and finally, a polyadenylation signal.
• The phenotypic architecture of the Herpesviridae family viruses characterizes these

viruses.
• Herepesvirus have a central viral core that contains a linear double stranded DNA.
This DNA is in the form of a torus, exemplified by a hole through the middle and the
DNA is embedded in a proteinaceous spindle
• The capsid is icosadeltahedral (16 surfaces) with 2-fold symmetry and a diameter of
100–120 nm that is partially dependent upon the thickness of the tegument.
• The capsid has 162 capsomeres.

• The three dimensional structure of the HHV-8 capsid was determined by cryo-electron
microscopy (EM) and was found to be composed of 12 pentons, 150 hexons, and 320
triplexes arranged as expected in the icosadeltahedral lattice with 20 faces; the capsids
are 125 nm in diameter
KAPOSI SARCOMA HPV-8
• A type of virus that causes Kaposi sarcoma (a rare cancer in which lesions grow in the
skin, lymph nodes, lining of the mouth, nose, and throat, and other tissues of the
body). Human herpesvirus 8 also causes certain types of lymphoma (cancer that
begins in cells of the immune system).
PATHOGENESIS
• HHV-8 is thought to be spread mainly by sexual interaction.

• Infects lymphocytes and develops a state of dormancy.
• -Inflammation or another trigger starts the lytic cycle -Inhibits the tumor suppressor
protein p53 -Cell lysis enables the virus to escape and invade nearby cells
• DNA fragments of HHV-8 have been detected in more than 95% of Kaposi's sarcoma
cases by PCR and anti-HHV-8 antibodies are detected in sera from patients with
Kaposi's sarcoma, regardless of HIV infection.
DIAGNOSTIC TEST
• PCR: used to detect the virus in various specimen such as tissue, blood, bone marrow,
saliva and semen.
PREVENTION AND TREATMENT
• Safe sexual practices, use condom

• For cancer treatment: surgery, radiation and chemotherapy
• ANtiviral drug ganciclovir targets HHV-* however is not effective for tumors
• If associated with AIDS, anti-retroviral medication

EPSTEIN-BARR VIRUS (EBV)
• Infectious mononucleosis is caused by the Epstein-Barr virus, which belongs to the

Lymphocryptovirus family.
• The Epstein-Barr virus (EBV) is a double-stranded DNA virus that belongs to the
Herpes family. EBV infection has an overall prevalence of over 90% worldwide.
• EBV can infect multiple cell types, including epithelial cells, B, T, and natural killer
(NK) lymphocytes, and mesenchymal cells such as smooth muscle cells.
• It consists of a double-stranded 172 Kb DNA genome, enclosed within an icosahedral

capsid, surrounded by a phospholipid rich envelope(1,3).
• Symptoms: Sore throat, fever, lymphadenopathy, hepatomegaly, splenomegaly, and
general malaise are all signs and symptoms of EBV. These normally go away after a
few weeks, but in some cases the malaise can last longer.
• Splenic hemorrhage and rupture, hepatitis, thrombocytopenia purpura with hemolytic
anemia are all complications of EBV infections.
PATHOGENESIS
• EBV can be obtained from the oropharynx of both symptomatic and healthy people,
and contaminated saliva can spread the virus to others.
• EBV can take anywhere from two weeks to two months to incubate. Infection is very
normal and leads to latency, much like the other herpes community viruses, and most
adults have antibodies to the virus. Infection in children under the age of five is almost
always asymptomatic. As the age at the time of infection rises to young adulthood, the
ratio of symptomatic to asymptomatic infections rises.
PATHOGENESIS
• In addition, the virus is becoming more widely known as a significant infectious agent
in transplant recipients. The initiation of a B-cell lymphoproliferative disorder or
lymphoma is the most serious clinical consequence of EBV infection in these patients.
• B cells and epithelial cells are infected; latency can be established.
• EBV can infect different cell types, including B cells and epithelial cells.
DIAGNOSTIC TEST
• Serologic Test: often used to diagnose EBV in the laboratory.

• Paul-Bunnell heterophile antibody test: an excellent rapid screening test for these
antibodies, while some false-positive reactions occur
TREATMENT
• The vaccine is currently being tested in clinical trials.
• -Chemotherapy, immunotherapy, bone marrow transplant, stem cell transplant, surgery, and
radiation for Burkitt's lymphoma
• -For Hodgkin's disease, early stage treatment includes chemo and radiation, while late stage
treatment includes only chemo.
• -Chemotherapy, radiation, and surgery for NPC

PRIONS
PRIONS
• PRION (INfectious PROtein)

• Stanley Prusiner
• Prnp gene
• Causative agents are protein molecules from within the cells of the host; no nucleic acid has been
found associated with them.
Carter, J., & Saunders, V. (2007). Chapter 26 Prions, Virology: Principles and Applications, 327-328 (1st ed.). Wiley.
PRIONS
• Prnp gene
It cycles between endosomes and the cell surface, where it is held in the plasma membrane by a
glycosyl-phosphatidyl-inositol anchor at its C terminus. It is found on many cell types, but
especially on cells of the central nervous system.
PRIONS
• the misfolded protein is largely resistant to proteinase K (heat resistant)

• renders the protein insoluble in nonionic detergents
• aggregate as fibrils, rods or other forms
PRIONS
• Onset in the UK of bovine spongiform encephalopathy (BSE), and its apparent transmission to
humans as variant Creutzfeldt-Jakob disease (vCJD).
• Characteristic pathology in the central nervous system, with parts of the brain becoming
vacuolated or spongey, in many cases also with extensive deposits of extracellular protein
fibrils or plaques but with no sign of inflammation.
• Different brain regions are affected by the various spongiform encephalopathies.
Dimmock, N., Easton, A., & Leppard, K. (2007). Chapter 22 Prion Diseases, Introduction to Modern Virology, 401-402. Wiley.
PRIONS REPLICATION
• It has been suggested that a form of ‘evangelism’ may be involved, whereby molecules of the
misfolded protein ‘convert’ normal protein molecules and cause them to misfold.
• SEED - an aggregate of a number of misfolded protein molecules
• accumulates in endosomes and lysosomes, and quantities build up especially in neurons.
PRIONS
Transmissible Spongiform Encephalopathies (TSE)
• encephalopathy means disease of the brain

• spongiform refers to the development of holes in the brain
• transmissible refers to the fact that the causative agent is infectious.
Carter, J., & Saunders, V. (2007). Chapter 26 Prions, Virology: Principles and Applications, 328 (1st ed.). Wiley.
PRIONS
PATHOLOGY
• Arise spontaneously, some are inherited, and some are acquired

• Entry may be through the digestive tract, followed by transport to the lymphoreticular system
• Replication takes place slowly but, because the misfolded protein is not degraded,
concentrations gradually build up.
• Long incubation period
PRIONS
SIGNS AND SYMPTOMS
• Loss of function of the brain

• personality changes
• depression
• memory problems
• difficulty in coordinating movements
• losing the ability to move or to speak
Dimmock, N., Easton, A., & Leppard, K. (2007). Chapter 22 Prion Diseases, Introduction to Modern Virology, 402. Wiley.
PRIONS
DISEASES IN HUMANS
• CJD - Creutzfeld–Jakob disease - most common, occurring throughout the world at an incidence of
about 1.7 cases per million people per year
• Familial CJD - families whose genomes encode certain amino acids at particular codons in the Prnp
gene
• Fatal familial insomnia - families whose genomes encode certain amino acids at particular codons
in the Prnp gene
PRIONS
DISEASES IN HUMANS
• CJD - Creutzfeld–Jakob disease - most common, occurring throughout the world at an

incidence of about 1.7 cases per million people per year
• Familial CJD & Fatal familial insomnia - families whose genomes encode certain amino acids
at particular codons in the Prnp gene
• Kuru & vCJD - acquired by ingesting prions
PRIONS
DIAGNOSTIC TEST
• Virus strains are defined by differences in the sequences of their nucleic acids, but if TSE
agents do not contain nucleic acids how can strains with different phenotypic characters be
explained?

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ONCOVIRUSES AND PRIONS

SANTOS, ARRION TOLENTINO, MELANIE VILLANUEVA, MICHAL

• Hepatitis B virus is a partially dsDNA enveloped virus that belongs to the

• Double stranded circular DNA, has 3200 bp in length

• (Eliason, 1940)Eliason, N. E. (1940). A Textbook. In American

• Jennings, C. Oncoviruses. https://www.vumc.org/chtn/sites/vumc.org.chtn/files/public_files/Oncoviruses!.ppt

• The HCV genome is a positive-sense RNA molecule of approximately 9500

• Treatment for virus = interferon + ribavirin, other antivirals + ribavirin, liver

• Jennings, C. Oncoviruses. https://www.vumc.org/chtn/sites/vumc.org.chtn/files/public_files/Oncoviruses!.ppt

• The Oncovirinae subfamily includes the human T-lymphotropic viruses HTLV-1,

• Typically, an EIA (enzyme immunoassay) test method is used initially to

• Jennings, C. Oncoviruses. https://www.vumc.org/chtn/sites/vumc.org.chtn/files/public_files/Oncoviruses!.ppt

• Prosultiamine, azacytidine, TDF (reverse-transcriptase inhibitor), and PCOANs are

• Jennings, C. Oncoviruses. https://www.vumc.org/chtn/sites/vumc.org.chtn/files/public_files/Oncoviruses!.ppt

• Cytology — the Papanicolaou test, commonly referred to as a Pap smear, is a useful

• Jennings, C. Oncoviruses. https://www.vumc.org/chtn/sites/vumc.org.chtn/files/public_files/Oncoviruses!.ppt

• Virus vaccination (Gardasil and Cervarix)

• Jennings, C. Oncoviruses. https://www.vumc.org/chtn/sites/vumc.org.chtn/files/public_files/Oncoviruses!.ppt

• The phenotypic architecture of the Herpesviridae family viruses characterizes these

• The capsid has 162 capsomeres.

• HHV-8 is thought to be spread mainly by sexual interaction.

• Safe sexual practices, use condom

• Jennings, C. Oncoviruses. https://www.vumc.org/chtn/sites/vumc.org.chtn/files/public_files/Oncoviruses!.ppt

• Infectious mononucleosis is caused by the Epstein-Barr virus, which belongs to the

• It consists of a double-stranded 172 Kb DNA genome, enclosed within an icosahedral

• Serologic Test: often used to diagnose EBV in the laboratory.

• The vaccine is currently being tested in clinical trials.

• -Chemotherapy, radiation, and surgery for NPC

• Jennings, C. Oncoviruses. https://www.vumc.org/chtn/sites/vumc.org.chtn/files/public_files/Oncoviruses!.ppt

• PRION (INfectious PROtein)

• the misfolded protein is largely resistant to proteinase K (heat resistant)

• encephalopathy means disease of the brain

• Arise spontaneously, some are inherited, and some are acquired

• Loss of function of the brain

• CJD - Creutzfeld–Jakob disease - most common, occurring throughout the world at an

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