Small Animal Retroviridae (Exam 2) Flashcards
What is special about retroviruses?
Retro = backwards
Reverse transcriptase: RNA dependent polymerase, creates complementary DNA, inserts backwards into host genome, no proof-reading
Used to detect RNA in PCR
How are retroviruses classified?
Nucleotide sequence
Core appearance based on transmission electron microscopy
Antigenic gag similarity
Pathophysiology: acute (rapidly) transforming, chronic (slowly) transforming), immunosuppressive
What is the general structure of retroviruses?
Enveloped with glycoprotein spikes (bi-lipid membrane from host cell)
Icosahedral capsid (contains, core proteins, RNA)
Diploid
Positive sense single stranded RNA
What genes do all retroviruses contain?
gag: group-specific antigen, capsid
pol: polymerase, integrase, reverse transcriptase
env: envelope, transmembrane surface proteins
+/- oncogenes
What is important about the envelope of retroviruses?
High mutation rate = antigenic variation
Envelope spike determines cell tropism and species specificity
Virus is unstable in environment, direct contact or cell transfer required
Describe general retrovirus replication
Virion contains 2 copies of the positive sense single stranded RNA genome
Reverse transcription of the viral RNA genome by reverse transcriptase produces dsDNA
dsDNA is transported to the nucleus where it integrates into host cell’s DNA (provirus)
Transcription is carried out by host to make viral mRNAs and vRNA genomes
Describe the steps of retrovirus replication
- cell binding- env to host
- fusion - core in cytoplasm
- reverse txn: RNA –> dsDNA +LTR
- nuclear entry
- integration via integrase (provirus in host genome)
- DNA transcription by host –> mRNA
- translation in cytoplasm, (a) proteins, (b) ssRNA
- env mRNA translocated
- env translation
- transmembrane proteins (env) assembled in golgi apparatus
- virion assembly
- budding
- release - infectious virions
What are the implications associated with permanent DNA integration in host cell?
Once host genome infected, host replicates viral genome (virus doesn’t have to replicate)
What is endogenization in regards to retroviruses?
Provirus integration into germline
Source of rapid mutations in host (evolution, tumorigenesis, immune development, autoimmune disease)
Source of virus recombination (may interact with exogenous virus)
What are the 2 types of retrovirus infections?
Transforming, oncogenic
Immunodeficiency, immune-mediated
What are the 2 types of retroviral oncogenesis?
Slowly transforming
Rapidly transforming
What are characteristics of slowly transforming oncogenesis?
Promoter inserted near/acting on host c-onc
Provirus randomly inserted into host genome
What are characteristics of rapidly transforming oncogenesis?
Contains v-onc
Need to be replication competent or get help from another virus
Define: c-onc
Cellular
Normal gene belonging to host, under biologic controls
Can be promoted by virus LTR
Define: v-onc
Viral
Mutated, upregulated/dysregulated by virus, no longer under normal controls
What are the important feline retroviruses?
Feline leukemia virus (FeLV)
Feline immunodeficiency virus (FIV)
What is the only horizontally infectious strain of FeLV?
A
What are the 2 disease routes of FeLV?
Immunodeficiency
Neoplasia
What are the most important strains of FeLV?
A, B