Vif-deficient HIV reverse transcription complexes (RTCs) are subject to structural changes and mutation of RTC-associated reverse transcription products.
Reverse transcription (RTn) in HIV-infected cells occurs in a nucleoprotein complex termed the reverse transcription complex (RTC). RTCs containing RT activity and integrase (IN) were shown to be heterogeneous in size and density on sucrose velocity and equilibrium gradients. WT and Vif-deficient (Deltavif) RTCs produced by infection with virus from permissive cells displayed similar sedimentation characteristics, while RTCs from Deltavif virus produced in non-permissive cells demonstrated a reduction in the major RTC form and more of the RTn products in rapidly sedimenting structures. APOBEC3G derived from virions did not co-sediment with RTCs, but RTCs from Deltavif infections showed elevated levels of mutations in RTn products, consistent with APOBEC3G and other mutational mechanisms. The most mutated transcripts were present within rapidly sedimenting RTCs. Thus, virus without functional vif, produced from non-permissive cells, forms abnormal RTCs that contain increased mutation of RTC-associated RTn products in newly infected target cells.
Carr
J M
JM
Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, Adelaide, South Australia 5000, Australia. jill.carr@imvs.sa.gov.au
Davis
A J
AJ
Coolen
C
C
Cheney
K
K
Burrell
C J
CJ
Li
P
P
D000071480:APOBEC-3G Deaminase; D002460:Cell Line; D002474:Cell-Free System; D003564:Cytidine Deaminase; D016346:Gene Products, vif / Q000172:deficiency* / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics*; D009700:Nucleoside Deaminases / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D048348:Reverse Transcription
D016346:Gene Products, vif; D046912:Multiprotein Complexes; D012097:Repressor Proteins; D054303:HIV Reverse Transcriptase; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase