Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Virology > Viruses and Neoplasia > Flashcards

Viruses and Neoplasia Flashcards

1
Q

What are the viruses that are associated with human cancer?

A

Exogenous retroviruses - Human T-cell lymphotropic virus (HTLV-1)
Positive stranded RNA viruses - Hepatitis C virus (HCV)
DNA viruses with retroviral features - Hepatitis B virus (HBV)
Large double stranded DNA viruses - Kaposi’s sarcoma herpes virus (KSHV also HHV8) and Epstein Barr Virus (EBV also HHV4)
Small double stranded DNA viruses - Human papillomavirus (HPV) and merkel cell polyomavirus (MCV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What viruses cause the most significant number of cancers?

A

Human papillomavirus, Hep C and Hep B

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How was causality of virus infection causing cancer proved?

A

Cell-free transmission: grinding up cells of benign epithelial tumour (wart) of rabbit and applying to another causes warts
Cell-free transmission: cell-free filtrate transmits sarcomatous chest tumour in hens (Rous sarcoma virus)
Observational studies: co-carcinogen (coal tar) stimulated cancer formation from a wart caused by papillomavirus in rabbits
Found tumour causing retroviruses in mammals (e.g. murine leukaemia virus and mouse mammary tumour virus (retroviruses) and murine polyomavirus)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How was the first human tumour virus discovered?

A

Found EBV by electron microscopy in cell lines derived from Burkitt’s lymphoma. Was investigated as the lymphoma was found in African patients and had strong geographical association. Researchers were lucky as tumour-causing viruses aren’t often found in the tumour as they virus doesn’t complete its productive life cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How was HBV identified as a tumour causing virus?

A

By epidemiological studies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How was HTLV-1 identified as a cancer causing virus?

A

Researches searched for reverse transcriptase activity in T cell lines. Idea from findings of a gibbon retrovirus that causes T cell leukaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How was HPV identified as a tumour causing virus?

A

Knew HPV caused warts, had seen a link between sexual activity and cervical cancer. Did hybridisation of HPV DNA with cancers and cell lines derived from cervical cancer and found high risk HPV DNA.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How was HCV identified as a tumour causing virus?

A

Probe cDNA expression library to find any non-human DNA sequences

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How was KSHV identified as a tumour causing virus?

A

cDNA from sarcoma and normal tissue was extracted and hybridisation was performed to identify differences. Herpes virus sequences found.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How was MCV identified as a tumour causing virus?

A

Merkel cell carcinoma found in immunosuppressed individuals suggesting a pathogenic origin. Deep sequence approach of cancer and non-infected cells followed by computer analysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How can viruses cause cancer?

A

Immunosuppression - if a cancer is related to immunosuppression may have a pathogenic cause. Indirect causation - immunosuppression (general or virus specific) can allow development of cancers caused by viruses. E.g. HIV allows deregulated gene expression by other cancer causing viruses such as HPV, KSHV and MCV
Chronic inflammation - tissue damage and repair leading to neoplasia by increasing chance of DNA damage and mutation e.g. HCV and HBV
Virus induced transformation - viruses have genes to deregulate the cell cycle and can cause cancer if expressed at wrong levels or times e.g. HPV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the general principles of viruses and neoplasia?

A

Inverse relationship between virus replication and cell transformation - viruses in tumours are pseudo latent. Get cancers when viruses infect non-permissive cells (e.g. SV40 in experimental animals, human adenoviruses in rats where early genes are expressed but whole virus replication isn’t supported)
Virus associated cancers often arise from chronic/longterm infections
Cancers that are caused by viruses are a biological accident and offer no fitness advantage for the virus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are Henle-Koch’s postulates?

A

How to prove causality of infectious agents driving cancer
- Agent should be present in every cause of disease under appropriate circumstances
- Agent shouldn’t be present in any other disease as a nonpathogenic agent
- Agene must be isolated from disease and induce disease in new animal
Doesn’t work for a lot of cancers caused by virus as virus is no longer produced. Also, cancer has many causes so won’t be in every disease. And, cancer is a rare outcome of a common infection. Can’t isolate the agent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are acutely transforming retroviruses?

A

Retroviruses with an oncogenic insertion. Normally a defective virus which isn’t replication competent on its own (has lost part of the replication machinery and needs a helper virus. RSV is an exception to this)
Can also have an oncogene as a viral product

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the classes of retroviruses in neoplasia?

A

Acutely transforming viruses (either have a host oncogene transducer or oncogene is a viral product)
Insertional mutagenesis viruses
Transactivating viruses
Immunosuppressive virsues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What does v-src do?

A

Is involved in signal transduction (a tyrosine kinase). ‘is mutated from the cellular version - lacks the tail that is phosphorylated to inhibit activity so is constituently active.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is JSRV and what does it do?

A

Jaagsiekte Sheep retrovirus, causes ovine pulmonary adenocarcinoma. A rare example of an oncogene that is a viral structural protein. Env. binds to hyaluronidase 2 leading to degradation and transmission of a growth signal and proliferation. As the virus infects secretory cells, it is thought that increased fluid production aids viral transmission (suggests there is an advantage to the virus for once)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Why is there age dependent resistance to ovine pulmonary adenocarcinoma?

A

Some retroviral infections require a mature immune system to clear - not the case here as endogenous expression of JRSV during foetal ontogeny means there is no immune response
Could be due to number of permissive cells in young sheep

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are slow transforming retroviruses?

A

Integrated provirus is close to a cellular oncogene. Insertion can up regulate cellular gene by insertional activation. Viruses are weakly oncogenic (slow transforming). Insertional sites are thought to be random but prefer active genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the small DNA tumour viruses?

A

Papillomaviruses (HPV, BPV, CRPV), polyomaviruses (HCV, SV40) and adenoviruses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Where do SV40 and human adenoviruses cause cancer?

A

Not in their natural host! Rodent cells are non-permissive for SV40 productive infection and human adenovirus infection but an abortive life cycle is supported in which a subset of viral genes are expressed.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What genes do small DNA tumour viruses use to drive cancer?

A

E6/E7 (papilloma)
T antigens (polyoma)
E1A/E1B (adeno)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What kinds of cancers to human papillomaviruses cause?

A

Nearly all cervical cancers
Majority of anal cancers
Some oropharyngeal tumours, vagina and penile cancer. Many papillomaviruses, only a subset cause cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the normal life cycle of small DNA viruses?

A

Adenoviruses are classified by serotype and infect humans early in life (asymptomatic). Can cause feverish colds and coughs and viral conjunctivitis
Polyomaviruses cause asymptomatic infection. During AIDS, a polyomavirus is associated with a neurodegenerative disease. Get other diseases in immunosuppressed
Papillomaviruses are classified by genotype and infect epithelial tissue. Either asymptomatic or get benign epithelial tumours (warts)
All persist in body in subclinical latent state and can be reactivated upon immunosupresions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How does evolution result in only low numbers of tumour viruses forming?

A

Viruses have been evolving with host for many years (especially papillomavirus), so most don’t cause problematic disease even though have cell cycle regulation genes. Only cause issues in specific hosts in which virus has evolved characteristics to escape host control. Normally it is beneficial for virus and host that it is carefully regulated so no uncontrolled proliferation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

How can human papillomaviruses be categorised?

A

5 categories - alpha, beta, gamma, mu and nu. Most medically important are alpha and include high risk HPV (16 and 18) and low risk viruses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How does HPV11 cause cancer?

A

Is a low risk alpha HPV virus. Mostly doesn’t cause cancer though in rare occasions, persistent infection can cause cancer e.g. individuals suffering from recurrent respiratory papiolloatosis

28
Q

How do beta HPV viruses cause cancer?

A

Mainly low risk viruses. In immunosuppressed individuals/those suffering from epidermodyspasia verruciformis. Immunosuppression allows deregulation of virus been expression.

29
Q

Describe infection of the population with high risk HPV

A

Are widespread in the population with 80% of people being infected at some point in their life time. Mostly the virus is cleared by the immune system after a few months/years. Cancer is caused in throughs who don’t clear infections and maintain deregulated expression of viral genes over a long period

30
Q

How does E6 in high risk HPV viruses drive cancer?

A

In normal HPV lifecycle, E6 binds p53 to prevent growth arrest (due to stimulation of division by another viral protein E7). High risk E6 binds p53 better than low risk. It recruits a ubiquitin ligase E6AP to degrade p53. High risk E6 has a PDZ motif at the C terminus that allows them to modify the function of PDZ cellular genes that are thought to maintain cellular polarity. It also suppresses genes involved in immune regulation such as IRF3, Tyk2

31
Q

How does E7 in high risk HPV virus drive cancer?

A

E7 normally targets p130 Rb that regulates cell cycle entry in upper epithelial layers. High risk E7 also targets all Rb including p105 and p107 which regulate cell cycle entry in the basal layer. Also suppress cellular proteins involved in immune regulation e.g. IRF3 and Tyk2

32
Q

What is the most common location of HPV cancers?

A

The cervical transformation zone - undergoes metaplasia at puberty (columnar cells that line the endocervix forms a protective multi-layered squamous epithelium) HPV infection can lead to development of cervical neoplasia. Abortive infection of HPV at the cerviicall transformation zone leading to cancer over time

33
Q

How is cervical cancer managed?

A

Cervical screening from the age of 25 picks up cytological abnormalities. Cancer develops over many years so this can be used to catch precancerous lesions. Can also do HPV DNA testing and looking for biomarkers in precancerous and cancerous lesions e.g. P16..
Have a vaccine. Originally just included HPV 16 and 18 but has been expanded to include 9 HPV types that protects against 90% of cervical cancers

34
Q

How do beta HPV cause cancer?

A

Potentially through a hit and run mechanism. In immunosuppressed individuals get non melanoma skin cancers due to deregulation of viral gene expression. Has proteins that interfere with DNA repair and UV induced apoptosis by targeting BAK for degradation. May cause skin cancers in normal skin and are variably present in cancers but are often win precancerous lesions - hit and run?

35
Q

How does cervical cancer progress?

A

Starts with a productive infection. Leads to CIN1 and CIN2 then CIN3 and cervical cancer. Facilitated by the integration of the HPV genome and loss of E2 regulation of E6/E7 leading to persistently high levels

36
Q

What is merkel cell carcinoma?

A

A neuroendocrine carcinoma of the skin. Is aggressive with 50% mortality rate. Risk factors are UV irradiation, immune suppression and old age (similar for beta HPV). Clonal integration of MCPyV genome is a causal factor (similar ago alpha HPV cancers).

37
Q

How does MCV cause MCC?

A

Integration of viral genome and continued expression of viral T antigen. Viral large T binds and inactivates pRb family members whilst its C terminal region binds viral ORI and aids replication (helicase activity). Small T antigen modifies eukaryotic initiation factor functions and inhibits degradation of large T by the protostome along with other cell cycle activators. Tumours often show down regulation of NHC-1 and TLR9 and NFkB.

38
Q

What retroviruses are associated with human cancer?

A

Complex retroviruses (i.e. lentiviruses or HIV) in which they encode gag, pol and env polyproteins and accessory proteins

39
Q

What are deltaretroviruses?

A

Transactivating retroviruses associated with neoplasia. Includes HTLVs 1-4 (human T lymphotropic viruses), STLVs (simian T lymphotropic viruses) and BLV (bovine leukosis virus)

40
Q

How was HTLV-1 discovered?

A

Clustering of adult lymphocytic T cell leukaemia cases suggested viral origen - found integration of HTLV-1 pro-viral sequences in cancer cells but not normal cells. Was also isolated from another patient suffering from cutaneous T cell lymphoma

41
Q

How does HTLV-1 spread within the host?

A

Is much less efficient than HIV in infecting CD4 cells (their target cell type), so instead of spreading virions between cells it spreads by driving clonal expansion of infected cells. Does cell-cell transmission (virological synapse) and clonal expansion. Is therefore more stable than HIV as it doesn’t rely on error prone reverse transcription (allows epidemiological tracing)

42
Q

How does HTLV-1 spread between hosts?

A

Mother to infant through breast milk
Parenteral transmission (meaning needles etc)
Sexual transmission

43
Q

How does ATLL arise from HTLV-1 infection?

A

Requires multiple cycles of T cell proliferation to allow accumulation of genetic errors that then lead to cancer. Infection in adulthood is less risky in terms of ATLL

44
Q

What is the difference between the type 1 and type 2 HTLV provirus?

A

Type 1 proviruses contains internal deletions but retains the pX and both LTRs
Type 2 provirus only has the 3’ LTR and the pX region. HBZ region is still retained, but ability to express Tax can be lost in cancer

45
Q

What is the structure of the HTLV-1 genome?

A

Is a retrovirus, so has 5’ long terminal repeat, then Gag, Pol and Env polyproteins. At 3’ end has a pX region in which accessory genes are encoded. At the 3’ terminus there is another LTR.

46
Q

What is the function of Tax in the induction of cancer in HTLV-1?

A

Is required for initiation of cancer but can then be lost. This loss may be beneficial as Tax is the primary target of cell-mediated immune responses against ATLL cells. Tax is a transcriptional regulator and induces viral gene expression from the 5’ LTR (which has a CRE like sequence called the Tax responsive element). It also binds CREB (a protein), transactivating genes with a CRE regulatory sequence. These are involved in growth, survival and apoptosis. Tax also activates NFkB through association with IKKgamma. Allows nuclear import of transcription factors. Tax also induces Akt (a regulator of cell survival and proliferation) phosphorylation by binding to PI3K

47
Q

What does HBZ do in induction of cancer in HTLV-1?

A

HBZ is maintained in all ATLL and also binds CREB. Thought to inhibit Tax function and also drive cell proliferation. Tax is highly immunogenic, and low levels of Tax are seen in infection (low levels and therefore evasion of CTLs are beneficial to clonal expansion). HBZ binds CREB and reduces its association with Tax leading to transcriptional repression of Tax. HBZ has a basic leucine zipper motive, and can heterodimerise with other bZip proteins that are components of the AP1 transcription factor complex to mediate transcription of cellular genes. HBZ mRNA can also interact with E2F family by a stem loop and promote proliferation

48
Q

How is HBV thought to cause cancer?

A

Multiple routes
The extensive cell proliferation or cirrhosis is thought to predispose to accumulation of genetic errors in infected cells with chronic inflammation raising local concentrations of potentially mutagenic superoxides and free radicals. DNA integration is also likely to be an important factor as all cancers have fragments of integrated DNA - thought to maybe be the first genetic hit.
Also, the HBV X gene is expressed in many human HCC - it is a transcriptional regulator of many cellular genes including protooncogenes (e.g. those in cell cycle regulation, DNA repair, signalling pathways) and has also been reported to inactivate p53

49
Q

Does HBV integrate at a specific site?

A

Not in humans - no evidence of insertional activation

In woodchuck, 90% in tegrate upstream of the myc protooncogene.

50
Q

How is HBV transmitted?

A

In endemic areas, from chronically infected mother to baby. Most children then get chronic infection so the virus persists
In non-endemic areas risk is from horizontal transmission e.g. drug use and sex (lower rates of chronicity)

51
Q

How is HCV transmitted?

A

Normally by contaminated blood, low risk through sexual/drug use or nosocomial (hospital).

52
Q

How can HBV infection be treated?

A

Course of interferon to induce virus clearance - not always effective, can be unpleasant (side effects)
Polymerase inhibitors to suppress viral replication, tend to relapse after treatment and get high rates of resistance with prolonged treatment

53
Q

How can HCV be controlled?

A

No vaccine. Give peglylated interferon + ribavarin (a nucleoside analogue). Is high cost, variable cure rates.

54
Q

How does HCV cause cancer?

A

Several viral proteins modulate signal transduction, stimulate the cell cycle and inhibit apoptosis. Are also involved in immune evasion. Likely to contribute to virus persistence and proliferation of infected cells
Immune mediated destruction of infected cells along with tissue regeneration and chronic local inflammation (like with HBV) are also likely to be damaging

55
Q

What diseases is EBV associated with?

A

Burkitt’s lymphoma (malignant B cell lymphoma of jaw and face)
Nasopharyngeal carcinoma
Hodgkin’s disease (another B cell lymphoma)
Implicated in some gastric and lymphoepithelial carcinomas

56
Q

What is infectious mononucleosis?

A

Glandular fever. Occurs when someone is infected with EBV for the first time as a teenager or young adult. EBV is ubiquitous, so many people (especially in developing countries) are infected as children which is asymptomatic. Is self limiting and non-fatal and is a result form an overactive immune response. Expansion of EBV specific T cells and NK cells results in swollen lymph nodes, liver and spleen. After recovery, EBV can persist in 1/1 million B cells and be reactivated to allow shedding of virus in saliva

57
Q

How does the mode of EBV infection link to disease associations?

A

Primary lytic infection is in the mucosal epithelium of nasopharynx and salivary glands. From here spreads to a latent infection in B cells that infiltrate local lymphatic tissue

58
Q

What is Burkitt’s lymphoma?

A

A malignant B cell lymphoma caused by EBV (in endemic areas - only 20% association in other places) that is particularly prevalent in children in certain parts of Africa and other. Risk factors are infection early in life and weak immune response. Restricted location suggests a co-factor, potentially Plasmodium falciparum. Characterised by deregulation of c-myc, often have a reciprocal translocation of chromosome 8 with other chromosomes.

59
Q

How does EBV facilitate development of Burkitt’s lymphoma?

A

BL is defined by a c-myc translocation. BL found in B cells which express latency 1 pattern of EBV genome expression including EBNA1 protein and EBERS (RNA molecules that modulate the immune system and prevent apoptosis). EBV infection is thought to enhance B cell proliferation increasing number of cells in which chromosome damage could occur as well as controlling apoptosis through LMP1/2 (latent associated membrane proteins, inhibit normal DNA repair). This effect is enhanced by P. falciparum (and/or HIV) as polyclonal B cell expansion occurs and T-cell response to control proliferation of B cells is inhibited. This predisposes to disease development

60
Q

What do EBV EBERS do in progression of cancer?

A

Non-coding RNAs that are expressed in latent EBV cells. Induce expression of IL-10 through IRF3 but not NFkB - suggests modulation of immune system (in BL), IGF-1 (gastric and nasopharyngeal carcinoma), IL-9 (T cells, an autocrine growth factor). EBER2 induces EL-6 which has a role in B cell growth transformation. EBERS bind PKR leading to resistance to PKR mediated apoptosis. EBER1 bindis RIG-I and activates downstream signalling for type 1 interferon expression. Secreted EBERs bind TLR3 and lead to induction of type 1 IFNs and inflammatory cytokines and immune activation - contributes to pathogenesis in active EBV infections.

61
Q

How is the profile of nasopharyngeal carcinoma?

A

Rare in western world,, common in south china, hong kong etc where it is 100% associated with EBV infection. Potential risk factors include certain HLA-A haplotypes and exposure to smoke or dust

62
Q

How does EBV facilitate the formation of nasopharyngeal carcinoma?

A

EBV infects an epithelial cell that already has mutations in driver genes (due to environmental insult). This allows EBV mediated cell transformation associated with latency II viral gene expression. Includes EBERs that are known about in Burkitt’s lymphoma as well as latent membrane proteins (LMP1 and 2) which activate signalling pathways NFkB, MAPK, JAK/STAT, PI3K/Akt which leads to proliferation.

63
Q

What is kaposi’s sarcoma?

A

Classically is a rare slow growing tumour of elderly men, has been seen as endemic in sub-Saharan africa (not AIDS related)
In AIDS patients, is a common cancer and is aggressive. Is more common in homosexuals with AIDS (compared to infected blood products), suggesting a sexually transmitted co-factor.
Polymorphic disease, high level of vascularity in tumours (bruise like appearance of tumours). Tumour cells are thought to babe lymphatic endothelial in origin

64
Q

What diseases is KSHV associated with?

A

Kaposi’s sarcoma
Primary effusion lymphoma (body cavity B cell tumour) and multi centric Castleman’s disease (hyperproliferation of B cells leading to non-cancerous tumours in lymph node tissue) (B cell disorders)

65
Q

What genes of KSHV are thought to contribute to tumourigenesis?

A

Vcyclin (constitutive activator of CDK6, associated with cytokinesis defects and polyploidy which activates p53 - need deletion to survive)
vFLIP (binds IKKy and inhibits IKKy’s inhibition of NFkB. NFkB activation induces cytokine expression. Also has anti-apoptotic roles)
vIL-6 (angiogenic, involved spindle proliferation and survival)
vBCL-2 (antiapoptotic)
vIRFs (inhibit p53 induces apoptosis)

Virology (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions