Horizontal gene transfer from human host to HIV-1 reverse transcriptase confers drug resistance and partly compensates for replication deficits.

Abstract:

:We investigated the origin and the effect of insertion D67D-THGERDLGPA within HIV-1 RT from a patient failing antiviral therapy. The insertion developed within the context of pre-existing NRTI and NNRTI mutations (M41L, L210W, T215Y and N348I). Concurrently, the NRTI mutations T69I and V118I and the NNRTI mutations K103N and Y181C were detected for the first time. High-level drug resistance (fold-changes≥50) and a good replication capacity (87% of wild-type) were observed, significantly higher than for the previous virus without insertion. The insertion was very similar to a region within human chromosome 17 (31/34 nucleotide identity), and had already been detected independently in a Japanese HIV-1 isolate. These results suggest that a particular sequence within human chromosome 17 is prone to horizontal gene transfer into the HIV-1 RT finger subdomain. This insertion confers selective advantage to HIV-1 by its contribution to multi-drug resistance and restoration of impaired replication capacity.

journal_name

Virology

journal_title

Virology

authors

Megens S,Vaira D,De Baets G,Dekeersmaeker N,Schrooten Y,Li G,Schymkowitz J,Rousseau F,Vandamme AM,Moutschen M,Van Laethem K

doi

10.1016/j.virol.2014.03.023

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

310-8

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(14)00105-6

journal_volume

456-457

pub_type

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