| Virologic characterization of HIV type 1 with a codon 70 deletion in reverse transcriptase. | |
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MedLine Citation:
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PMID: 17496561 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Zixin Hu; Hiroyu Hatano; Sarah P Hammond; Danielle Smith; Mary Wild; Soumi Gupta; Jeannette Whitcomb; Robert C Kalayjian; Barbara Gripshover; Daniel R Kuritzkes |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Journal of acquired immune deficiency syndromes (1999) Volume: 45 ISSN: 1525-4135 ISO Abbreviation: J. Acquir. Immune Defic. Syndr. Publication Date: 2007 Aug |
Date Detail:
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Created Date: 2007-08-31 Completed Date: 2007-10-10 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100892005 Medline TA: J Acquir Immune Defic Syndr Country: United States |
Other Details:
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Languages: eng Pagination: 494-500 Citation Subset: IM; X |
Affiliation:
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Section of Retroviral Therapeutics, Brigham and Women's Hospital, and Division of AIDS, Harvard Medical School, Boston, MA, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenine
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analogs & derivatives,
therapeutic use Antiviral Agents / pharmacology Cell Line, Transformed Codon / genetics Deoxycytidine / analogs & derivatives, pharmacology Didanosine / pharmacology Dideoxynucleosides / pharmacology, therapeutic use Drug Resistance, Viral HIV Infections / drug therapy, virology* HIV Reverse Transcriptase / genetics* HIV-1 / drug effects, enzymology, genetics* Hela Cells Humans Lamivudine / pharmacology Phosphonic Acids / therapeutic use Point Mutation Reassortant Viruses / drug effects Reverse Transcriptase Inhibitors / pharmacology, therapeutic use |
| Grant Support | |
ID/Acronym/Agency:
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K24 RR16482/RR/NCRR NIH HHS; P30 AI60354/AI/NIAID NIH HHS; R01 AI42567/AI/NIAID NIH HHS; U01 AI068636/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antiviral Agents; 0/Codon; 0/Dideoxynucleosides; 0/Phosphonic Acids; 0/Reverse Transcriptase Inhibitors; 0/abacavir; 0/emtricitabine; 107021-12-5/tenofovir; 134678-17-4/Lamivudine; 69655-05-6/Didanosine; 73-24-5/Adenine; 951-77-9/Deoxycytidine; EC 2.7.7.49/HIV Reverse Transcriptase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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