Virus Life Cycle and PCR for Integrated DNA

Virus Life Cycle

• The virus initially binds to the host cell.
• Fusion and virus entry occur subsequently.
• Reverse transcription of viral RNA into viral DNA occurs.
• Viral DNA integrates into the feline DNA.
• Transcription and viral genome production follow integration.
• The viral genome is translated then.
• Assembly and budding of progeny viruses conclude the cycle.

PCR Test for Integrated Viral DNA

• Proviral DNA is viral DNA integrated into the cat's genome.
• PCR can detect proviral DNA.
• Primers 1 and 2 target specific regions (LTR, gag, pol, env) within the proviral DNA.
• Amplifying the specific region confirms proviral DNA presence.

Viral LTR Drives Expression of Viral Genes

• Proviral DNA contains LTR sequences (long terminal repeats).
• LTR acts as a promoter for viral genes.
• Viral promoter activates transcription of various viral genes.
• Viral genes encode proteins important for viral replication (capsid, replication enzymes, envelope).

Oncogenic Mechanism 1: Viral Insertional Activation of a Cellular Proto-Oncogene

• Normal gene expression, cellular promoter is off.
• Provirus insertion can activate proto-oncogenes.
• Aberrant expression of oncogene occurs.
• Insertion may cause cellular promoter turning on.
• Oncogenes contribute to unregulated cell growth.
• Cancer formation is the result of this.

Oncogenic Mechanism 2: Viral Insertional Inactivation of a Tumor Suppressor Gene

• Normal gene expression, cellular promoter is off.
• Tumor suppressors are inactivated by proviral insertion.
• Inactivation causes loss of tumor suppressor function.
• Insertion may cause cellular promoter turning on.
• This deregulation of function can lead to cancer.

Oncogenic Mechanism 3: Viral Acquisition of Cellular Oncogenes (Transduction)

• Viruses can carry oncogenes from other sources.
• Oncogenes can be inserted at random points in retroviral genomes.
• Involves interaction of defective virus (FeSV) with helper virus (FeLV).
• Helper virus provides viral proteins needed for the defective virus to replicate properly.

Viral Genomes Also Change During Replication

• Viral polymerase (reverse transcriptase) is prone to errors.
• Frequent duplications and mutations in LTR and SU envelope proteins occur.
• Errors result in altered pathogenesis.

Internal LTR Duplications Impact Pathogenesis

• Internal LTR (long terminal repeat) duplication patterns vary.
• Duplication patterns associated with different pathologies.
• Duplicated LTR region's associated with different cell types and diseases.
• Variations are linked to altered pathogenesis.

Viral Genomes Also Mutate During Replication

• Viral polymerase (reverse transcriptase) has errors during replication.
• Frequent mutations in LTR and SU protein.
• Mutation consequences result in altered pathogenesis.

SU Protein Responsible for Entry

• Viruses utilize host cell proteins for entry.
• Receptor use is virus-specific.
• FeLV uses SU protein to bind host cell receptors specifically.

Subgroup Viruses Use Different Cellular Receptors

• FeLV subgroups arise from recombination and mutations.
• Different FeLV subgroups, use distinct host receptors.
• Receptor use influences pathogenesis.
• Only some cells express the receptors.

FeLV Types

• FeLV-A: Associated with immunosuppression.
• FeLV-B: Associated with neoplasia.
• FeLV-C: Associated with anemia, linked to heme export receptor issues and depletion of erythroid precursors.

Chronic FeLV-C Infection Causes Fatal Anemia

• The receptor for FeLV-C is FLVCR1.
• Normal function is heme export.
• FeLV-C infection disrupts receptor function.
• Results in erythrocyte precursor depletion.

Infection with T-Cell-Tropic FeLV Induces Immunodeficiency (FeLV-FAIDS)

• T-cell-tropic FeLV (mutation/recombination in SU protein)
• Binds to receptors similar to FeLV-B but necessitates a co-factor for entry.
• Co-factor expression is restricted to lymphoid cells.
• T-cells perish after infection.

FeLV Vaccines

• Vaccines lessen progressive infections.
• Available in whole killed, subunit, and recombinant canary pox vector formats.
• Potential fibrosarcoma side effects are reduced by peripheral administration.
• High-risk cats are vaccinated.

Key Concepts

• FeLV causes proliferative and degenerative illnesses.
• FeLV molecular biology is relevant in pathogenesis.
• Transmission happens through contact or biting.
• Infected cats can have abortive, regressive, or progressive infections.
• Vaccines reduce the probability of progressive diseases.
• FeLV test types depend on the time period following infection.