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Spring, 2004 Lecture Outline

3/18 RETROVIRIDAE


Retrovirus intro
: large family, getting larger as more discovered

retro = backward
reverse transcriptase = RNA-directed DNA polymerase- copies RNA into DNA

retro-'s differ from all other RNA viruses- can incorporate into host genome
only virus family known to simultaneously transform & produce progeny
3 subfamilies: oncoviruses; spumaviruses; lentiviruses

human retroviruses:

oncoviruses- HTLV-1: helper T-cell leukemia, also fibroblasts
HTLV-2, variant of HTLV-1

lentiviruses- HIV

structure: Rous sarcoma virus (RSV)- prototype (infects birds)

icosahedral; envelope c peplomers; matrix & core
RNA: R regions at both ends- repeated seq for dimerization
long terminal repeats(LTR) of viral DNA- from U5 (5') & U3 (3') end seq.- important for promotion, enhancement, regulation

reverse transcriptase:

most prefer Mg++ to Mn++ as cation (one prefers Mn++)
carry many molec of pol in virion, instead of on-site translation

3 fxns: complimentary DNA

nuclease- digests RNA of DNA/RNA hybrid
makes "plus" DNA strand to form dsDNA = provirus

some have 4th fxn: integrase- dsDNA ligated into host genome

steps after reverse transcription:

1. viral DNA supercoils -> enters nucleus
2. integrates c genome at some site (appears random)
3. host DNA-directed RNA polymerase II transcribes to form viral RNA

transcription & translation:

LTRs contain: promotors & enhancers; ribosome binding sites; cellular protein binding sites; termination codons; poly(A) signal

assembly:

38 S RNA + grp-specific viral proteins -> cell membrane, pick up glycoproteins; during maturation & budding- dimers of 70 S RNA reform


defective retroviruses: smaller RNA, half normal size

pseudotypes: c simultaneous infection of competent & defective

latency:

1. transformation c/out replication; transcription occurs
2. no transcription or replication

Viral DNA replication & transformation are mutually exclusive

permissive cells vs. nonpermissive cells

However, RNA replication and transformation can occur together
therefore RNA tumor viruses can reproduce in transformed cells

immunological consequences of transformation

 

Next week:

Hepadnaviridae [dsDNA virus] uses reverse transcriptase- see CRC, ch 6 & appropriate parts of Wagner, including ch 21, & on-line

Small genome DNA viruses- Microviridae & Inoviridae- see CRC, ch 5 & appropriate parts of Wagner, including ch 17, & on-line

 

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 Updated 1/25/04 by thatcher@sonoma.edu