Virologic characterization of HIV type 1 with a codon 70 deletion in reverse transcriptase.

TitleVirologic characterization of HIV type 1 with a codon 70 deletion in reverse transcriptase.
Publication TypeJournal Article
Year of Publication2007
AuthorsHu Z, Hatano H, Hammond SP, Smith D, Wild M, Gupta S, Whitcomb J, Kalayjian RC, Gripshover B, Kuritzkes DR
JournalJ Acquir Immune Defic Syndr
Volume45
Issue5
Pagination494-500
Date Published2007 Aug 15
ISSN1525-4135
KeywordsAdenine, Antiviral Agents, Cell Line, Transformed, Codon, Deoxycytidine, Didanosine, Dideoxynucleosides, Drug Resistance, Viral, Emtricitabine, HeLa Cells, HIV Infections, HIV Reverse Transcriptase, HIV-1, Humans, Lamivudine, Organophosphonates, Point Mutation, Reassortant Viruses, Reverse Transcriptase Inhibitors, Tenofovir
Abstract

We identified a deletion at codon 70 (Delta70) of HIV-1 reverse transcriptase (RT) occurring together with L74V and Q151M mutations in a sample from a tenofovir (TFV)- and abacavir (ABC)-treated patient with extensive prior antiretroviral treatment. To investigate the characteristics of this mutant, we studied the drug susceptibility, relative infectivity, and fitness of viruses carrying Delta70 and associated RT mutations. The Delta70, L74V, and Q151M mutations were introduced into Hxb2 RT by site-directed mutagenesis and expressed in HIV-1 recombinants. The Delta70 mutation increased resistance to lamivudine and emtricitabine alone and in combination with various resistance mutations and augmented resistance to ABC and didanosine when present together with L74V. A recombinant virus expressing RT from the original clinical viral sample (Delta70-PRT) exhibited greater fitness than one in which the deletion had been repaired (K70-PRT). The Delta70 mutation also increased fitness of Hxb2 wild-type and 74V and Q151M mutants. Recombinants carrying Delta70-PRT showed greater relative infectivity in the presence of ABC (but not TFV) compared with K70-PRT recombinants. These results show that Delta70 enhances resistance to certain purine and pyrimidine analogues and contributes to multinucleoside resistance in the appropriate viral genetic background.

DOI10.1097/QAI.0b013e31806ada48
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID17496561
Grant ListK24 RR16482 / RR / NCRR NIH HHS / United States
P30 AI60354 / AI / NIAID NIH HHS / United States
R01 AI42567 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States