B8: retroviruses Flashcards
What is unique about retroviral genomes?
Retroviruses have RNA genomes that are reverse-transcribed into double-stranded DNA by the enzyme Reverse Transcriptase (RT).
What is the basic replication strategy of a retrovirus?
The genomic RNA is converted into cDNA, which integrates into the host genome; then, the provirus is transcribed to produce new viral RNAs.
What are the three main groups in the old retrovirus classification?
Oncoretroviruses (oncogenic or benign), Lentiviruses (“slow” viruses like HIV), and Spumaviruses (foamy viruses).
How are retroviruses classified in the revised system?
They are divided into the Orthoretrovirinae (which include oncornaviruses and lentiviruses) and the Spumaretrovirinae (foamy viruses).
Give examples of retroviruses from different genera.
Deltaretrovirus: Human T Cell Leukemia Virus (HTLV); Lentivirus: HIV, EIAV, Visna; Spumavirus: Foamy viruses causing benign infections.
What does the gag gene encode?
It encodes the group-specific antigen proteins, which are precursors to internal structural proteins such as matrix (MA), capsid (CA), and nucleocapsid (NC).
What is the function of the pro gene in retroviruses?
It encodes the viral protease, which cleaves polyproteins into functional proteins.
What does the pol gene produce?
It encodes enzymes like Reverse Transcriptase (RT) and Integrase (IN).
What does the env gene encode?
It encodes the envelope glycoproteins that form the viral surface, which mediate cell attachment and entry.
How is a simple retrovirus genome organized?
It follows a basic 5′–gag–pro–pol–env–3′ arrangement. Complex retroviruses also encode additional accessory genes.
What is the typical size and morphology of a retrovirus particle?
Retrovirus virions are 80–120 nm in diameter, have a spherical shape, and a phospholipid envelope studded with glycoprotein knobs.
What composes the retroviral RNP?
The RNP consists of two copies of the (+) sense RNA genome, capped and polyadenylated, bound by ~2000 molecules of NC protein and enclosed within a capsid shell.
What are the key features of the retroviral genome?
The genome is positive-sense RNA, 7–10 kb long, capped, polyadenylated, and includes a bound tRNA (typically tRNA^Lys) at the primer binding site (PBS).
How do retroviruses typically enter a host cell?
Entry is mediated by Env proteins that bind specific cellular receptors (e.g., HIV binds CD4, sometimes with a co-receptor), followed by fusion of the viral and cellular membranes.
What distinguishes lentiviral entry?
Lentiviruses (like HIV) can infect non-dividing cells due to their ability to transport the intact capsid into the cytoplasm and through the nuclear pore.
What are the two enzymatic activities of Reverse Transcriptase (RT)?
RT has RNA-dependent DNA polymerase activity and RNase H activity, which degrades RNA in RNA:DNA hybrids.
How is cDNA synthesis initiated in retroviruses?
A host tRNA binds to the PBS, and RT synthesizes a short DNA copy that includes the R and U5 regions at the 5′ end.
What occurs during the first template switch in reverse transcription?
The newly synthesized R:U5 DNA plus tRNA hybrid is transferred from the 5′ to the 3′ end of the RNA template, allowing extension of the negative-strand cDNA.
How is the negative-strand cDNA completed?
RT extends the cDNA along the RNA template while RNase H degrades most of the RNA, leaving behind a small segment (the PPT).
What initiates positive-strand cDNA synthesis?
The PPT-bound RNA acts as a primer, and after synthesis, a second template switch occurs, resulting in a complete double-stranded cDNA flanked by identical long terminal repeats (LTRs).
How does the cDNA enter the host nucleus?
The cDNA, within the pre-integration complex (PIC) bound to integrase, is transported into the nucleus (lentiviruses can do this via the nuclear pore).
How does retroviral integrase function during integration?
Integrase cleaves two nucleotides from the 3′ ends of cDNA, makes staggered cuts in the host DNA, ligates the viral DNA into the host genome, and the gaps are filled by host enzymes.
What is the result of retroviral integration?
The integrated form of the viral genome, known as the provirus, becomes transcriptionally active and serves as a template for viral mRNA production.
What roles do the LTRs play after integration?
The 5′ LTR acts as a promoter for RNA polymerase II, and the 3′ LTR functions as a polyadenylation and transcription termination signal.
How is viral mRNA processed in retroviruses?
Unspliced RNA serves as mRNA for gag–pol proteins and is packaged as genomic RNA, while spliced RNAs encode env and accessory proteins.
How do retroviruses express gag-pro-pol from a single mRNA?
They use mechanisms such as leaky scanning, ribosomal frameshifting, and alternative start codons to produce polyproteins.
How are retroviral polyproteins processed?
The gag and gag–pol polyproteins are cleaved post-translationally by the viral protease (pro), releasing functional proteins including RT and IN.
What happens during retroviral capsid assembly?
The genomic RNA (with bound tRNA) is packaged into a capsid formed by NC and other proteins, guided by a packaging signal on the RNA.
How is the mature retroviral virion assembled and released?
Interactions between gag–pol and env proteins coordinate assembly at the plasma membrane with the help of host ESCRT machinery for budding; final maturation occurs post-budding.
What are the major steps in the retroviral life cycle?
Binding → Fusion → Reverse Transcription → Integration → Transcription/Translation (replication) → Assembly → Budding.
