In:
Open Forum Infectious Diseases, Oxford University Press (OUP)
Abstract:
HIV is not efficiently transmitted between hosts, and selection of viral variants occurs during the process of sexual transmission. The factors that confer selective advantage at the transmission bottleneck remain incompletely understood. We explored whether differences in the Rev-Rev Response Element (RRE) regulatory axis of HIV affect transmission fitness, since functional variation in the Rev-RRE axis in different viral isolates has been shown to affect replication kinetics and relative expression of many HIV proteins. Methods Single genome HIV sequences were identified from nine linked participant pairs near the time of female-to-male transmission. Using a rapid flow-cytometric assay, we analyzed Rev-RRE functional activity of primary isolates. Results Functional Rev-RRE activity was significantly lower in recipient viruses compared to the corresponding donor viruses. In six of nine transmission events, recipient virus Rev-RRE activity clustered at the extreme low end of the range of donor virus activity. Rev-RRE pair activity was an unpredictable product of component Rev and RRE activity variation. Conclusions These data indicate selection pressure on the Rev-RRE axis during female-to-male sexual transmission. Variation in the activity of the Rev-RRE axis may permit viral adaptation to different fitness landscapes and could play an important role in HIV pathogenesis.
Type of Medium:
Online Resource
ISSN:
2328-8957
DOI:
10.1093/ofid/ofad486
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2023
detail.hit.zdb_id:
2757767-3
