B10: endogenous RVs Flashcards
What distinguishes retroviruses that cause cancer?
They carry an extra viral oncogene (v-onc) in addition to the core retroviral genes, which is “pirated” from a cellular gene (c-onc) and drives cell proliferation.
How is a viral oncogene (v-onc) typically different from its cellular counterpart?
v-onc is usually constitutively “on” (switched on permanently) with no feedback control, leading to uncontrolled cell growth.
What are the five classes of retroviral oncogenes?
They include regulators of cell proliferation such as growth hormones, receptors for extracellular growth signals, G proteins, protein kinases, and transcription factors.
Which virus, recovered by Peyton Rous over 100 years ago, provided the first evidence of viral oncogenesis?
Rous sarcoma virus (RSV) recovered from a chicken sarcoma.
What oncogene does Simian Sarcoma Virus encode and what is its function?
It encodes v‑sis, a homolog of the PDGF growth factor.
Which oncogene is carried by avian erythroblastosis virus, and what cellular function does it mimic?
It carries v‑erb, which is related to the Epidermal Growth Factor Receptor.
What does the v‑ras oncogene from murine sarcoma virus encode?
A small G protein (GTPase) that functions in signal transduction.
What is the role of v‑src in Rous sarcoma virus?
v‑src encodes a tyrosine kinase that is constitutively active (lacking negative regulatory regions).
What does v‑mos from Moloney murine virus encode?
A serine–threonine kinase involved in cell cycle regulation.
What is the function of v‑myc encoded by MC29 avian myelocytoma virus?
It encodes a transcription factor that regulates cell proliferation.
Why are many retroviruses carrying oncogenes replication defective?
They often have deletions in one or more core genes and express the oncogene as a Gag‑Onc fusion; they require co-infection with a helper virus for replication.
How can retroviruses without oncogenes cause cancer?
Through proviral insertional mutagenesis, where integration near a cellular proto-oncogene (c-onc) upregulates its expression, or by producing novel transforming factors, including transforming Env proteins.
How do proviral long terminal repeats (LTRs) contribute to cellular transformation?
They can act as promoters/enhancers for nearby c-onc genes, leading to fusion transcripts, stabilized mRNA, and increased oncogene expression.
What is proviral insertional mutagenesis?
: It is when integration of the provirus disrupts normal gene function (e.g., in gatekeeper genes like Rb) or alters splicing, leading to deregulated cell division.
What is the function of the HTLV-1 Tax protein?
Tax is a multifunctional regulatory protein (≈40 kDa) that drives viral gene expression and can stimulate cellular transformation.
How can retroviral Env proteins induce transformation?
For example, Friend spleen focus-forming virus (SFFV) expresses an Env protein (gp55) that binds and activates the erythropoietin receptor, leading to erythroid hyperplasia.
What is the role of JSRV Env protein in transformation?
It activates cell-signaling pathways that contribute to cellular transformation.
What are endogenous retroviruses?
ERVs are retroviral sequences that have integrated into the germline and are inherited as part of the host genome.
How do HERVs contribute to genetic variability?
They provide multiple insertion sites for recombination, leading to duplications, deletions, and chromosomal rearrangements, influencing species evolution.
What is Syncytin-1 and why is it important?
It is a captive Env protein derived from a HERV that mediates fusion of placental cytotrophoblasts to form the syncytiotrophoblast, essential for placental development.
Can HERVs produce virus particles?
Most HERVs are defective due to mutations; however, HERV‑K subtypes can produce virus-like particles (VLPs) in certain tissues and tumors.
What diseases are HERVs potentially linked to?
Oncogenesis, autoimmunity, inflammation, diabetes, and antiviral resistance.
: How might HERVs contribute to cancer?
HERV RNA and proteins, such as HERV‑K Rec and Np9, may be upregulated in cancers like teratocarcinoma, seminoma, and melanoma, stimulating transformation.
Which autoimmune condition has been linked with HERV upregulation?
Inflammatory lesions in multiple sclerosis have shown increased HERV RNA and protein expression.
What is the proposed link between HERVs and neurological disorders?
Elevated levels of specific HERV RNA and proteins have been found in the brain tissue of patients with schizophrenia.
Why are porcine endogenous retroviruses (PERVs) a concern in xenotransplantation?
PERVs can produce particles that infect human cells, posing a potential risk when pig tissues or organs are transplanted into humans.
What are LTR retrotransposons and how are they related to retroviruses?
They are transposable elements that replicate via an RNA intermediate, are related to retroviruses but lack the env gene, so they have no extracellular phase.
What is the difference between Type I and Type II transposable elements?
Type I elements (retrotransposons) use an RNA intermediate, whereas Type II elements (DNA transposons) do not.
What components make up a retroviral gene therapy vector?
A retroviral DNA vector containing LTRs and a packaging signal (Ψ) with the gene of interest, and a packaging cell line that supplies gag, pol, and env proteins.
What are the advantages of lentiviral vectors and how are pseudotypes used for safety?
Lentiviral vectors (often based on HIV‑1) efficiently infect non-dividing cells and integrate stably. They are designed without most HIV genes and can be pseudotyped (e.g., with VSV‑G protein) to avoid using the native HIV envelope, enhancing safety.
