Retroviridae: RNA Viruses

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Questions and Answers

What is the defining genomic feature of retroviruses that fundamentally dictates their replication strategy and interaction with the host cell?

  • A single-stranded positive-sense RNA genome that is directly translated into viral proteins.
  • A segmented double-stranded RNA genome that undergoes reassortment during replication.
  • A single-stranded positive-sense RNA genome that is reverse transcribed into DNA for integration into the host cell’s genome. (correct)
  • A double-stranded DNA genome that integrates directly into the host cell’s DNA.

Which enzymatic activity is essential for retroviruses to establish a persistent infection in a host cell?

  • Reverse transcriptase, for converting viral RNA into DNA.
  • Integrase, for incorporating the viral DNA into the host genome. (correct)
  • RNA polymerase, for transcribing viral RNA.
  • Protease, for maturation of viral proteins.

Which of the following is a characteristic shared by both persistent infections and oncogenic potential in retroviruses?

  • The requirement for a highly lytic replication cycle that rapidly destroys host cells.
  • The production of a potent toxin that directly induces cellular damage and disease.
  • The integration of the provirus into the host cell genome, leading to long-term presence or potential cellular transformation. (correct)
  • The ability to evade the host's immune response through frequent antigenic variation.

How does the integration of a retroviral provirus lead to oncogenesis?

<p>By disrupting or activating cellular genes involved in growth control, leading to uncontrolled proliferation. (D)</p> Signup and view all the answers

What is the primary genetic difference between transducing and cis-activating retroviruses concerning oncogenesis?

<p>Transducing viruses carry an oncogene in their genome and cis-activating viruses do not. (D)</p> Signup and view all the answers

Given that retroviruses integrate their genetic material into the host cell's genome, which mechanism of oncogenesis would least likely involve direct alteration of the host cell's DNA sequence?

<p>Oncogenesis mediated by essential retroviral proteins (Trans-activating) (C)</p> Signup and view all the answers

In the context of retroviral oncogenesis, how do cis-activating and trans-activating mechanisms differ in their immediate effect on the host cell's gene expression?

<p><em>cis</em>-activating mechanisms involve the physical insertion of viral DNA near a proto-oncogene, while <em>trans</em>-activating mechanisms involve viral proteins influencing gene expression without direct DNA insertion nearby. (B)</p> Signup and view all the answers

Considering the three mechanisms of retrovirus-induced cell transformation, in which mechanism would the timeline for the development of clinical disease most likely be the longest?

<p>Oncogenesis mediated by essential retroviral proteins (trans-activating), because it does not involve direct alteration of the host cell's DNA sequence. (A)</p> Signup and view all the answers

How does the genome organization of Flaviviruses differ from that of Retroviruses, influencing their respective replication strategies and potential for integration into the host genome?

<p>Flaviviruses have a positive-sense RNA genome that does not require reverse transcription, whereas Retroviruses require reverse transcription for integration. (D)</p> Signup and view all the answers

A key difference between Flaviviruses and Retroviruses lies in their mechanism of replication and integration. What is the most significant implication of this difference in terms of the host cell?

<p>Flaviviruses, not integrating into the host DNA, can be cleared more readily by the host immune system, while Retroviruses, integrating into the host DNA, can establish persistent infections. (A)</p> Signup and view all the answers

How does the strategy of transmission generally differ between Flaviviruses and Retroviruses?

<p>Flaviviruses primarily rely on vector-borne transmission, while Retroviruses typically transmit through direct contact or vertically. (B)</p> Signup and view all the answers

How does the non-cytopathic nature of some Flavivirus strains complicate disease management and control?

<p>It allows for persistent asymptomatic infections, facilitating viral spread by infected individuals who are unaware of their condition. (D)</p> Signup and view all the answers

Given Bovine Viral Diarrhea Virus (BVDV) can cause either transient or persistent infections in cattle, what is a critical determinant that differentiates the outcome of these two types of infections?

<p>The age of the animal at the time of infection and its ability to mount an effective immune response before or during gestation. (D)</p> Signup and view all the answers

What is the most significant implication of persistent BVDV infections in cattle populations?

<p>It results in animals that serve as continuous reservoirs of the virus, shedding it throughout their lives and infecting other animals. (D)</p> Signup and view all the answers

How can mucosal disease arise in persistently infected calves with BVDV, and what is its significance in terms of disease pathogenesis?

<p>Mucosal disease arises when the noncytopathic BVDV mutates to a cytopathic biotype, or the animal is superinfected with a cytopathic strain of BVDV, leading to severe erosive lesions. (A)</p> Signup and view all the answers

What is the primary difference in genome organization that accounts for the tissue tropism switch seen in feline enteric coronavirus (FECV) leading to feline infectious peritonitis (FIP)?

<p>FECV replicates in intestinal epithelial cells, while FIPV results from mutations in the S gene that can infect macrophages. (D)</p> Signup and view all the answers

How does antibody-dependent enhancement (ADE) contribute to the unique pathogenesis observed in feline infectious peritonitis (FIP)?

<p>Antibodies enhance viral entry into macrophages, leading to increased viral replication and a hyperinflammatory response. (C)</p> Signup and view all the answers

What is the molecular basis for the tissue tropism switch observed in the transition from feline enteric coronavirus (FECV) to feline infectious peritonitis virus (FIPV)?

<p>Mutations in the spike (S) protein that allow for entry into macrophages, combined with systemic spread. (C)</p> Signup and view all the answers

What is the most accurate description of the role of antibody-dependent enhancement (ADE) in the pathogenesis of Feline Infectious Peritonitis (FIP)?

<p>ADE promotes the uptake of antibody-bound virus into macrophages, enhancing viral replication and exacerbating inflammation. (D)</p> Signup and view all the answers

Considering that Feline Infectious Peritonitis (FIP) results from a mutation of Feline Enteric Coronavirus (FECV), what is the primary reason that an antibody response, initially intended to neutralize the virus, paradoxically worsens the disease?

<p>The antibodies bind to the virus and facilitate its uptake into macrophages, where the virus replicates more efficiently, exacerbating the inflammatory response (antibody-dependent enhancement). (D)</p> Signup and view all the answers

Given the role of both tissue tropism and antibody-dependent enhancement (ADE) in the pathogenesis of Feline Infectious Peritonitis (FIP), which of the following scenarios would likely lead to the most severe FIP outcome?

<p>A cat that is infected with a strain of FECV that readily infects and replicates in macrophages, and also develops a strong antibody response. (A)</p> Signup and view all the answers

Which of the following strategies leverages the unique replication mechanism of retroviruses to achieve targeted gene editing in eukaryotic cells?

<p>Engineering a retroviral vector to deliver a gene-editing tool like CRISPR-Cas9, which then integrates into the host genome. (A)</p> Signup and view all the answers

Which aspect of retroviral reverse transcription poses the greatest challenge for maintaining the genetic stability of retroviral vectors used in gene therapy?

<p>The error-prone nature of reverse transcriptase, leading to high mutation rates and potential loss of therapeutic gene function or unintended oncogenic effects. (A)</p> Signup and view all the answers

What is a primary safety concern associated with the use of retroviral vectors in gene therapy, considering their mechanism of integration into the host cell genome?

<p>The risk of random integration leading to insertional mutagenesis, which can disrupt essential genes or activate oncogenes, potentially causing cancer. (A)</p> Signup and view all the answers

What strategy has been employed to reduce or eliminate the risk of insertional mutagenesis in retroviral vector-mediated gene therapy?

<p>Engineering retroviral vectors with integrase enzymes that preferentially target safe harbor loci in the genome, minimizing the risk of disrupting essential genes. (A)</p> Signup and view all the answers

Why do persistent infections with non-cytopathic BVDV strains complicate disease eradication efforts more than transient infections?

<p>Persistently infected animals continuously shed the virus without showing obvious signs, making them difficult to identify and remove from the population. (C)</p> Signup and view all the answers

Given the role of macrophages in the pathogenesis of FIP, which therapeutic approach would most directly target disease progression?

<p>Developing drugs that block the uptake of virus-antibody complexes into macrophages, preventing ADE. (A)</p> Signup and view all the answers

What is the MOST critical factor that determines whether a calf infected with BVDV will develop a persistent infection?

<p>The calf's age at the time of infection; calves infected before development of immunocompetence may become persistently infected. (B)</p> Signup and view all the answers

How does antigenic variation (mutations in viral protein structure) affect the long-term control of flavivirus infections, such as those caused by Bovine Viral Diarrhea Virus (BVDV)?

<p>Antigenic variation hinders vaccine efficacy and diagnostic accuracy, requiring frequent updates to vaccines and tests to match circulating strains. (C)</p> Signup and view all the answers

Considering the persistent nature of retroviral infections, what is the MOST significant challenge in developing curative therapies for retrovirus-associated diseases, such as those caused by HIV?

<p>The virus integrates into the host cell genome forming a provirus, making it difficult to eradicate without harming the host cells. (A)</p> Signup and view all the answers

You're working in a veterinary diagnostic lab and receive a sample from a calf suspected of having Bovine Viral Diarrhea Virus (BVDV). Which diagnostic technique would be MOST appropriate for identifying a persistently infected (PI) animal, given that PI animals may not show obvious clinical signs?

<p>RT-PCR on a blood sample, detecting viral RNA. (D)</p> Signup and view all the answers

Which feature of retroviruses is the basis for the development of diagnostic tools to detect specific pathogens in molecular diagnostics?

<p>The process of reverse transcription, which can be exploited to amplify viral RNA. (A)</p> Signup and view all the answers

Given the differences in genomic structure, what might be the main rationale for why there is not a live attenuated vaccine for Retroviruses, while there are for Flaviviruses?

<p>Retroviruses integrate into the host genome meaning this could still happen in a attenuated virus whereas Flaviviruses replicate differently. (B)</p> Signup and view all the answers

Following a diagnosis of Feline Infectious Peritonitis (FIP) in a multi-cat household, what strategy is LEAST useful as an intervention to protect the other cats?

<p>Administering a coronavirus vaccine to all cats. (A)</p> Signup and view all the answers

Knowing that Bovine Viral Diarrhea Virus (BVDV) can cause both transient and persistent infections, what is the MOST effective long-term strategy for controlling BVDV in a cattle herd?

<p>Vaccinate all animals in the herd annually with a modified live or killed vaccine, in conjunction with testing and removal of persistently infected (PI) animals. (C)</p> Signup and view all the answers

Why are persistent infections with BVDV more challenging to control than transient infections within a cattle population?

<p>PI shed viruses and have minimal signs where it will spread quickly. (B)</p> Signup and view all the answers

Flashcards

Retroviridae

Family of viruses with ss(+)RNA genome and DNA intermediate in replication.

Reverse Transcriptase

An enzyme unique to retroviruses that synthesizes DNA from an RNA template, crucial for viral replication.

Provirus

Viral DNA integrated into the host cell genome.

Retroviral Infections

Disease characterized by persistent infections and potential tumor development.

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Proto-oncogene

A normal gene that regulates cell growth; when mutated or overexpressed, it can cause cancer.

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Oncogene

A mutated proto-oncogene that drives uncontrolled cell growth, leading to cancer.

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Oncogene Capture (transducing)

Acquiring an oncogene from the host cell genome

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Insertional Activation (cis-activating)

Insertion of viral DNA near a proto-oncogne, activating it's expression.

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Transactivation (trans-activating)

Upregulation of a host cellular proto-oncogene due to viral proteins.

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Flaviviridae

Family of viruses with ss(-)RNA genome and icosahedral symmetry.

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Viral Transmission

Viral spread from mother to offspring (vertical) or between individuals (horizontal).

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BVDV

Bovine Viral Diarrhea Virus.

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Persistent Viral infections

An infection where the virus is present long-term without clearing.

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"Plain Jane" BVDV infection

A form of BVDV characterized by inappetence, depression, and diarrhea.

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Mucosal Disease

A consequence of persistent BVDV involving erosions of the oral and intestinal tract.

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Teratogenic effects

Birth defects caused by infection during pregnancy.

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Coronaviridae

Family of viruses with ss(+)RNA genome and helical nucleocapsid.

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Tissue tropism switch

Switch in the type of cells a virus infects.

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FECV

Initial infection with Feline Enteric Coronavirus.

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FIPV

A mutation of FECV that causes a deadly systematic spread.

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Antibody-Dependent Enhancement (ADE)

When antibodies enhance rather than neutralize viral infection.

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Study Notes

Lecture 6: RNA Viruses I

Retroviridae Family Properties

  • Possesses single-stranded positive-sense RNA, with a DNA intermediate.
  • It is an enveloped virus containing a helical nucleocapsid.
  • Uses reverse transcriptase.
  • Integrates provirus into the host cell genome.
  • Causes persistent, pathogenic infections.
  • Diseases include immune deficiency and oncogenesis in the host.
  • There are 2 subfamilies, 7 genera, and multiple unique species.

Retroviridae Taxonomy

  • Alpharetrovirus includes Avian leukosis virus, Avian sarcoma virus, Avian myeloblastosis virus, and Rous sarcoma virus.
  • Betaretrovirus includes Mouse mammary tumour virus and Jaagsiekte sheep retrovirus.
  • Gammaretrovirus includes Feline leukemia virus, Feline sarcoma virus and Reticuloendotheliosis virus.
  • Deltaretrovirus includes Bovine leukemia virus and Human T-lymphotropic viruses 1 and 2.
  • Epsilonretrovirus includes Walleyed dermal sarcoma virus.
  • Lentivirus includes Human and Simian immunodeficiency viruses, Maedi/visna virus, Caprine arthritis-encephalitis virus, Equine infectious anemia virus, Feline and Bovine immunodeficiency virus.
  • Spumaretrovirinae includes Spumavirus, causing foamy cytopathology in cell culture and not associated with clinical disease.
  • Can cause oncogenic (+/- immune suppression) or immunodeficiency/immune-mediated (+/- neoplasia secondary to immunodeficiency) diseases.

Retrovirus-Induced Oncogenesis

  • A proto-oncogene refers to a gene encoding for proteins that regulate cell growth and differentiation that can become an oncogene potentially causing cancer.
  • Proto-oncogenes control cell growth and are highly regulated.

Mechanisms of Cell Transformation by Retroviruses

  • There are 3 primary mechanisms of cell transformation by retroviruses.
  • Oncogene capture where (c-onc -> v-onc) is transducing results in the rapid induction of clinical disease.
  • Insertional mutations cause activation of adjacent c-onc causing cis-activation and resulting in intermediate timeline of clinical disease.
  • Oncogenesis mediated by essential retroviral proteins leads to trans-activation resulting in a slow timeline of disease.

Flaviviridae Properties

  • Contains a single-stranded negative-sense RNA genome.
  • Enveloped with icosahedral symmetry (spherical).
  • Causes persistent (asymptomatic) infections.
  • Exhibits vertical vs. horizontal transmission patterns.
  • May have non-cytopathic vs. cytopathic strains.
  • Can have different disease syndromes.
  • The family consists of four genera and many species.

Flaviviridae Taxonomy

  • Orthoflavivirus includes Yellow fever, Japanese encephalitis, Dengue and Zika viruses, West Nile virus, Tickborne encephalitis and Kyasanur Forest disease viruses, as well as Powassan virus.
  • Pestivirus includes Bovine viral diarrhea virus (BVDV), Classical swine fever virus and Border disease virus.
  • Includes the Hepacivirus and Pegivirus genera.

Persistent Infection with Bovine Viral Diarrhea Virus (BVDV)

  • Results in subclinical disease.
  • "Plain Jane BVDV infection" can cause pyrexia and oral ulcerations, inappetence, depression, decreased milk production, excessive nasal/ocular secretions or diarrhea.
  • Can cause BVDV infection and immunosuppression.
  • Additionally, causes Bovine respiratory disease and pneumonia.
  • May result in Hemorrhagic syndrome (Severe BVDV infection).

Coronaviridae Family Properties

  • Has single-stranded positive-sense RNA.
  • Enveloped and has a helical nucleocapsid.
  • Undergoes tissue tropism switch, where it can change from intestinal epithelium to macrophages.
  • Causes antibody-dependent enhancement of disease.
  • The Feline enteric coronavirus (FECV) can transform to Feline infectious peritonitis virus (FIPV).

Tissue Tropism in Coronaviridae

  • Low virulent biotype: mild diarrhea
  • The tissue tropism of Feline enteric coronavirus occurs in the intestinal epithelium resulting in an enterotropic effect.
  • The tissue tropism of Feline infectious peritonitis has an affinity for macrophages, resulting in a pantropic (systemic) effect that is highly virulent and associated with severe systemic disease.

Antibody-Dependent Enhancement of Disease in FIP

  • Results in a diminished ability of immune cells to clear the virus.

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