Evidence for the acquisition of multi-drug resistance in an HIV-1 clinical isolate via human sequence transduction.
Insertions in HIV-1 reverse transcriptase's fingers subdomain can enhance chain terminator excision and confer resistance to multiple nucleoside analogs. Inserts that resemble flanking sequences likely arise by local sequence duplication. However, a remarkable variety of non-repeat fingers insertions have been observed. Here, molecular epidemiology, sequence analyses and mechanistic modeling were employed to show that one Japanese isolate's RT fingers insert likely resulted from non-homologous recombination between virus and host sequences and the transductive copying of 37 nucleotides from human chromosome 17. These findings provide evidence that human sequence transduction can, at least rarely, contribute to genetic and phenotypic variation in pandemic HIV.
Takebe
Yutaka
Y
Laboratory of Molecular Virology and Epidemiology, AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Telesnitsky
Alice
A
D019380:Anti-HIV Agents / Q000494:pharmacology; D001483:Base Sequence; D002648:Child; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D015658:HIV Infections / Q000235:genetics* / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D017434:Protein Structure, Tertiary; D014161:Transduction, Genetic
D019380:Anti-HIV Agents; D054303:HIV Reverse Transcriptase