[04.01a] Oncogenic Viruses (Part 1) V2.pdf

Multifactorial

Carcinogenesis is described as what kind of process?

Definitive etiology

Cancers caused by viruses have what type of etiology?

Vaccines

What specific measure can be taken to stop cancer from happening, given knowledge of its viral origin?

15-20%

What percentage of cancers have a viral etiology?

Preventable

What is the consequence of knowing that 15-20% of cancers have a specific viral etiology?

Hard to plate in agar plates

Why are oncogenic viruses difficult to study compared to bacteria?

Whole animal studies

What research method is performed to study oncogenic viruses when they are difficult to plate?

Host-virus interactions and how the virus transforms normal animal cells

What are two things that whole animal studies allow researchers to observe?

Cultured cells

What method is performed to study cancer when whole animal studies are not always viable?

McCoy or HeLa cell lines

What two specific cell lines are used to study cancer with live culture plates?

Nucleic acid and protein coat (capsid)

What are the components of a naked virus?

Capsomeres

What is the protein coat (capsid) of a naked virus composed of?

An envelope

What additional layer distinguishes an enveloped virus from a naked virus?

Dr. Macabulos

Whose instruction was it to review the replication of positive sense and negative sense in DNA and RNA?

Initiators

Human cancer viruses are described as only acting as what role in tumor formation?

Necessary to start carcinogenesis but not sufficient to finish carcinogenesis

How does the role of human cancer viruses relate to the overall process of carcinogenesis?

Immune system of the host and tropism of the virus

What are two examples of host-related factors that necessitate a multi-factorial approach to carcinogenesis?

Cellular tumor suppressor genes

DNA viruses are involved with what type of genes in starting tumors?

They produce proteins that disrupt cell growth of the host

How do proteins produced by DNA viruses interfere with the host cell?

Cellular oncogenes (or proto-oncogenes)

RNA viruses are involved with what type of genes in starting tumors?

Normal cells

Where are proto-oncogenes found?

Highly oncogenic

Which type of RNA virus directly transforms the host cell by having oncogenes at the cellular level?

Mostly in animals

Where are highly oncogenic RNA viruses mostly observed?

Weakly oncogenic

Which type of RNA virus uses indirect mechanisms to alter the host mechanism to be conducive to carcinogenesis?

Mostly in humans

Where do weakly oncogenic RNA viruses comprise the majority of observed RNA viruses?

Obligate intracellular parasites and Tropism to certain cells

What are the two required properties of human cancer viruses?

DNA or RNA, single-stranded or double-stranded, and enveloped or unenveloped

By what three general characteristics can viruses be classified?

PARvoviruses

Which single-stranded DNA viruses are represented by the mnemonic PAR?

Papillomaviruses, Polyomaviruses, and Adenoviruses

Which three families of double-stranded unenveloped DNA viruses are represented by the mnemonic PaPA?

Hepadnaviruses, Herpesviruses, and Poxviruses

Which three families of double-stranded enveloped DNA viruses are represented by the mnemonic He Has POX?

Hepadnaviridae (HBV) and Herpesviridae

What are two families of enveloped, double-stranded DNA viruses?

Papillomaviridae (Human Papillomavirus) and Polyomaviridae (BK, JC, SV40)

What are two families of unenveloped, double-stranded DNA viruses that are carcinogenic to humans?

Adenoviridae

Which double-stranded unenveloped DNA virus is carcinogenic primarily to animals?

Parvoviridae

Which family represents single-stranded unenveloped DNA viruses?

Adenovirus and SV40

Which two animal viruses are important in research because they help understand the mechanism of DNA viral transformation?

Flaviviridae and Retroviridae

What are the two primary families of oncogenic RNA viruses listed?

Hepatitis C Virus (HCV)

Which oncogenic virus belongs to the Flaviviridae family?

HTLV (Human T Lymphocyte Virus) and HIV (Human Immunodeficiency Virus)

What are two oncogenic viruses belonging to the Retroviridae family?

DNA virus (Hepadnaviridae)

The Hepatitis B Virus (HBV) belongs to which major viral classification?

RNA virus (Flaviviridae)

The Hepatitis C Virus (HCV) belongs to which major viral classification?

G1 (Gap 1) Phase

Which phase of the cell cycle involves the cytoplasm doubling?

S Phase

Which phase of the cell cycle involves the synthesis of DNA and chromosomes?

G2 (Gap 2) Phase

Which phase of the cell cycle involves the assembly of components like spindle fibers?

M Phase (Mitosis)

Which phase of the cell cycle involves cell division?

Checkpoints

What are the points where the cell cycle stops to verify that the right materials or chromosomes are produced?

Apoptosis or cellular changes

What happens to cells with errors detected at the cell cycle checkpoints?

Proto-oncogenes

What genetic elements act as the "Gas pedal" in the cell cycle?

Tumor suppressor genes

What genetic elements act as the "Brakes" in the cell cycle, inhibiting it at checkpoints?

p53 and pRB

What are two common examples of tumor suppressor genes?

Activation of cellular oncogenes and inactivation of tumor suppressor genes

What are the two molecular mechanisms by which carcinogenesis happens?

RNA viruses

Which type of virus achieves carcinogenesis primarily through the activation of cellular oncogenes?

Overexpressed, expressed at the wrong time, or expressed in the wrong tissue type

What three conditions can lead to proto-oncogenes becoming oncogenes?

Promoter Insertion Sequence

What mechanism allows an RNA virus to insert a sequence before the proto-oncogenic sequence, activating it?

Needs to be in a specific place in the chromosome

What is the required location for the Promoter Insertion Sequence to promote transcription?

Virus enhancer sequence

What viral sequence can be located anywhere on the chromosome and may reduce or increase transcription?

DNA viruses

Which type of virus achieves carcinogenesis primarily through the inactivation of tumor suppressor genes?

Oncoproteins

What do DNA viruses create by forming complexes with tumor suppressor genes?

Continuous cell division and tumor formation

What is the result of complexes formed by DNA virus oncoproteins causing the cell to lose its "brakes"?

pRb (retinoblastoma protein)

What is a well-known tumor suppressor protein that DNA viruses target, often resulting in retinoblastoma in children?

G1 Checkpoint

Which cell cycle checkpoint does a DNA virus complex stop pRB from acting upon, leading straight to the synthesis phase?

Regulates cell growth and promotes cell cycle kinase

What are two functions of P53?

Tyrosine-specific kinase

What is the function of the proto-oncogene src?

Growth factor, mitogen

What is the function of the proto-oncogene sis?

Nuclear transcription factor

What is the function of the proto-oncogene myc?

Mutated growth factor

What is the function of the proto-oncogene erB?

Growth factors

src, sis, myc, and erB are all considered what?

Proto-oncogenes

What are the normal versions of oncogenes called?

Uncontrolled growth of cells

Oncogenes are responsible for what process?

RNA virus studies

The understanding of oncogenes derived from studies involving which type of virus?

Negative regulators of cell growth

What is the fundamental role of tumor suppressor genes?

DNA virus studies

The understanding of tumor suppressor genes derived from studies involving which type of virus?

Chronicity of an infection

What viral factor makes the host cell more liable to lose its control mechanisms?

Modifying the MHC of the host

What viral evasion strategy, seen in CMV and adenovirus, makes it harder for APCs to recognize the virus?

Restricted expression of viral genes during latency

What viral evasion strategy is seen in EBV?

Mutation of viral antigens

What viral evasion strategy, seen in HIV, prevents detection by antibodies?

Inhibition of antigen processing

What viral evasion strategy is seen in EBV?

Infection and suppression of other essential immune cells

What evasion strategy is seen in HIV, causing problems in B-cells and T-cells?

Viral DNA remains in the host

What mechanism of DNA viruses involves part of the viral genome being integrated into the host cell chromosome?

Direct acting gene (transforming genes)

Which mechanism of action involves the transforming gene itself altering the cell?

Indirect-acting gene

Which mechanism of action involves altering the expression of pre-existing genes?

Permissive cells

What cell type supports the growth and replication of the virus, leading to lysis but not transformation?

DNA viruses

Permissive cells are usually associated with which type of virus?

Nonpermissive cells

What cell type cannot support viral growth and replication and undergoes transformation into tumor cells?

RNA viruses

Nonpermissive cells, which transform the host instead of killing it, are mostly associated with which type of virus?

The host and the virus

What two factors determine if a cell is permissive for a specific virus type?

The virus

What is considered the sole initiator of carcinogenesis, despite its multifactorial nature?

No normal homologs in cells

What genetic characteristic contrasts DNA viruses with RNA viruses (which have proto-oncogenes)?

Oncoproteins

What do DNA viruses produce that form complexes with normal cell proteins to alter function?

Polyomavirus SV40

What is an example of a DNA virus that produces large T and small t antigens?

p53 and pRB

What two cellular proteins are targets of Polyomavirus SV40 oncoproteins?

TP53

What gene produces the protein p53?

RB gene

What gene produces the protein pRB?

Stop the cell cycle and induce apoptosis

What is the normal function of p53 when a mutation is present?

Cell cycle continues

What happens when viral oncoproteins form a complex with p53, preventing apoptosis?

Large T and small t antigens

What are the oncoproteins produced by Polyomavirus SV40?

E6 and E7

What are the oncoproteins produced by Human papillomavirus?

E1A

What is the oncoprotein produced by Adenovirus?

LMP1

What is the oncoprotein produced by Herpesvirus EBV?

p53 and pRb

What are the cellular targets of Polyomavirus SV40 Large T antigen?

PP2A

What is the cellular target of Polyomavirus SV40 Small t antigen?