B11: viruses that can cause cancer Flashcards
How Is p53 Regulated?
p53 levels are controlled by MDM2, a ubiquitin ligase that targets p53 for proteasomal degradation.
What Is the Role of E2F and Rb in Cell Cycle Control?
E2F promotes the transition from G1 to S phase, while the retinoblastoma protein (Rb) inhibits this process; inactivation of Rb (e.g., by viral proteins) can release E2F and promote cell division.
What Types of Viruses Are Associated with Tumors?
Many tumor-associated viruses are DNA viruses (often with nuclear involvement) or retroviruses; they typically are non-lytic and either replicate as episomes or integrate into the host genome.
How Can a Viral Genome Exist in an Infected Cell?
It may exist as an episome (a DNA molecule replicating independently) or integrate into the host genome (as in retroviruses or papillomaviruses).
How Does Viral Infection Contribute to Cancer?
Viral infection is one “hit” among many (e.g., smoking, obesity, alcohol) that cause cell injury and predispose cells to transformation.
What Are Oncoviruses?
Oncoviruses are tumor-associated viruses that can contribute to cancer development either by carrying viral oncogenes or by influencing the expression of cellular proto-oncogenes.
What Are Retroviruses with Oncogenes?
These retroviruses encode a viral oncogene (v-onc) in addition to their core genes; v-onc is derived from a cellular proto-oncogene (c-onc) and drives cell proliferation.
How Do Viral Oncoproteins Typically Function?
They are usually regulators of cell proliferation that become permanently “on” without normal feedback control.
Name the Five Classes of Retroviral Oncogenes.
Growth hormones, receptors for extracellular growth signals, G proteins (signal transducers), protein kinases, and transcription factors.
What Did Peyton Rous Discover Over 100 Years Ago?
Peyton Rous recovered Rous sarcoma virus (RSV) from a chicken sarcoma, providing the first evidence of viral oncogenesis.
Give Examples of Specific Retroviral Oncogenes.
Simian Sarcoma Virus: v‑sis (PDGF growth factor)
* Avian Erythroblastosis Virus: v‑erb (EGF receptor)
* Murine Sarcoma Virus: v‑ras (small GTPase)
* Rous Sarcoma Virus: v‑src (tyrosine kinase)
* Moloney Murine Virus: v‑mos (serine–threonine kinase)
* MC29 Avian Myelocytoma Virus: v‑myc (transcription factor)
Why Are Many Retroviruses with Oncogenes Replication Defective?
They often have deletions in one or more core genes and express their oncogene as a Gag–Onc fusion, so they require a helper virus to replicate.
How Do Retroviruses Without Oncogenes Cause Cancer?
Through insertional mutagenesis—proviral integration can alter the expression of nearby cellular proto-oncogenes (c-onc) or disrupt tumor suppressor genes.
What Role Do Proviral LTRs Play in Cellular Transformation?
LTRs act as promoters/enhancers that can upregulate adjacent c-onc genes, create fusion transcripts, or stabilize c-onc mRNAs, promoting uncontrolled cell growth.
How Can Proviral Insertional Mutagenesis Lead to Cancer?
By disrupting normal gene function (e.g., in gatekeeper genes like Rb) or altering alternative splicing to remove regulatory domains from proto-oncoproteins.
What Is an Example of a Novel Regulatory Protein Produced by a Retrovirus?
The HTLV-1 Tax protein, a multifunctional regulatory protein that drives viral gene expression and contributes to cellular transformation.
How Can Retroviral Env Proteins Contribute to Transformation?
Certain Env proteins (e.g., from Friend spleen focus-forming virus and Jaagsiekte sheep retrovirus) can activate cellular receptors (like the erythropoietin receptor) and signaling pathways that promote proliferation.
What Are Endogenous Retroviruses (ERVs)?
ERVs are retroviral sequences that have integrated into the germline and are inherited as part of the host genome.
How Do Human Endogenous Retroviruses (HERVs) Contribute to Genetic Variability?
HERVs provide insertion sites for recombination, leading to duplications, deletions, and chromosomal rearrangements that contribute to evolutionary change.
What Role Does Syncytin-1 Play in Human Development?
Syncytin-1, derived from an ERV Env protein, mediates the fusion of placental cytotrophoblasts to form the syncytiotrophoblast, which is essential for placental development.
Can HERVs Produce Virus Particles?
Most HERVs are defective due to accumulated mutations; however, certain HERV-K subtypes can produce virus-like particles (VLPs) in specific tissues or tumors.
What Diseases Have Been Associated with HERV Expression?
HERVs have been linked to oncogenesis, autoimmunity, inflammation, diabetes, and antiviral resistance. They are upregulated in cancers, multiple sclerosis, schizophrenia, and more.
What Are Retroviral Gene Therapy Vectors?
They are engineered systems that use retroviral DNA vectors (containing LTRs and a packaging signal) along with packaging cell lines supplying gag, pol, and env to deliver therapeutic genes into target cells.
What Are Lentiviral Vectors and Their Advantages?
Lentiviral vectors (often derived from HIV-1) efficiently infect non-dividing cells and allow stable gene expression via integration into the host genome. They are designed to be replication-defective and safe.
