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• W2605862165 abstract "ABSTRACT There are marked differences in the spread and prevalence of HIV-1 subtypes worldwide, and differences in clinical progression have been reported. However, the biological reasons underlying these differences are unknown. Gag-protease is essential for HIV-1 replication, and Gag-protease-driven replication capacity has previously been correlated with disease progression. We show that Gag-protease replication capacity correlates significantly with that of whole isolates ( r = 0.51; P = 0.04), indicating that Gag-protease is a significant contributor to viral replication capacity. Furthermore, we investigated subtype-specific differences in Gag-protease-driven replication capacity using large well-characterized cohorts in Africa and the Americas. Patient-derived Gag-protease sequences were inserted into an HIV-1 NL4-3 backbone, and the replication capacities of the resulting recombinant viruses were measured in an HIV-1-inducible reporter T cell line by flow cytometry. Recombinant viruses expressing subtype C Gag-proteases exhibited substantially lower replication capacities than those expressing subtype B Gag-proteases ( P < 0.0001); this observation remained consistent when representative Gag-protease sequences were engineered into an HIV-1 subtype C backbone. We identified Gag residues 483 and 484, located within the Alix-binding motif involved in virus budding, as major contributors to subtype-specific replicative differences. In East African cohorts, we observed a hierarchy of Gag-protease-driven replication capacities, i.e., subtypes A/C < D < intersubtype recombinants ( P < 0.0029), which is consistent with reported intersubtype differences in disease progression. We thus hypothesize that the lower Gag-protease-driven replication capacity of subtypes A and C slows disease progression in individuals infected with these subtypes, which in turn leads to greater opportunity for transmission and thus increased prevalence of these subtypes. IMPORTANCE HIV-1 subtypes are unevenly distributed globally, and there are reported differences in their rates of disease progression and epidemic spread. The biological determinants underlying these differences have not been fully elucidated. Here, we show that HIV-1 Gag-protease-driven replication capacity correlates with the replication capacity of whole virus isolates. We further show that subtype B displays a significantly higher Gag-protease-mediated replication capacity than does subtype C, and we identify a major genetic determinant of these differences. Moreover, in two independent East African cohorts we demonstrate a reproducible hierarchy of Gag-protease-driven replicative capacity, whereby recombinants exhibit the greatest replication, followed by subtype D, followed by subtypes A and C. Our data identify Gag-protease as a major determinant of subtype differences in disease progression among HIV-1 subtypes; furthermore, we propose that the poorer viral replicative capacity of subtypes A and C may paradoxically contribute to their more efficient spread in sub-Saharan Africa." @default.
• W2605862165 created "2017-04-28" @default.
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• W2605862165 date "2017-07-01" @default.
• W2605862165 modified "2023-10-15" @default.
• W2605862165 title "Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are Consistent with Intersubtype Differences in HIV-1 Disease Progression" @default.
• W2605862165 cites W1564320023 @default.
• W2605862165 cites W1849393705 @default.
• W2605862165 cites W1909386356 @default.
• W2605862165 cites W1948557594 @default.
• W2605862165 cites W1964895626 @default.
• W2605862165 cites W1968838260 @default.
• W2605862165 cites W1970301294 @default.
• W2605862165 cites W1972828904 @default.
• W2605862165 cites W1982106400 @default.
• W2605862165 cites W1983683921 @default.
• W2605862165 cites W1989508688 @default.
• W2605862165 cites W1991729182 @default.
• W2605862165 cites W1999868284 @default.
• W2605862165 cites W2003070335 @default.
• W2605862165 cites W2006977189 @default.
• W2605862165 cites W2009082439 @default.
• W2605862165 cites W2010561000 @default.
• W2605862165 cites W2014365515 @default.
• W2605862165 cites W2014893636 @default.
• W2605862165 cites W2015237638 @default.
• W2605862165 cites W2023420720 @default.
• W2605862165 cites W2027298939 @default.
• W2605862165 cites W2028972269 @default.
• W2605862165 cites W2032402861 @default.
• W2605862165 cites W2044296969 @default.
• W2605862165 cites W2044388759 @default.
• W2605862165 cites W2051807614 @default.
• W2605862165 cites W2062956368 @default.
• W2605862165 cites W2063583714 @default.
• W2605862165 cites W2063953070 @default.
• W2605862165 cites W2066354913 @default.
• W2605862165 cites W2068253484 @default.
• W2605862165 cites W2068568287 @default.
• W2605862165 cites W2075322672 @default.
• W2605862165 cites W2081885109 @default.
• W2605862165 cites W2087092404 @default.
• W2605862165 cites W2088933904 @default.
• W2605862165 cites W2089135598 @default.
• W2605862165 cites W2091694152 @default.
• W2605862165 cites W2094193440 @default.
• W2605862165 cites W2096932129 @default.
• W2605862165 cites W2099272076 @default.
• W2605862165 cites W2103546861 @default.
• W2605862165 cites W2107329104 @default.
• W2605862165 cites W2110299975 @default.
• W2605862165 cites W2112507995 @default.
• W2605862165 cites W2114596116 @default.
• W2605862165 cites W2116745209 @default.
• W2605862165 cites W2116956383 @default.
• W2605862165 cites W2123404862 @default.
• W2605862165 cites W2123584222 @default.
• W2605862165 cites W2124409966 @default.
• W2605862165 cites W2124996928 @default.
• W2605862165 cites W2125586839 @default.
• W2605862165 cites W2134847258 @default.
• W2605862165 cites W2137085164 @default.
• W2605862165 cites W2137447301 @default.
• W2605862165 cites W2139213642 @default.
• W2605862165 cites W2140193569 @default.
• W2605862165 cites W2143067006 @default.
• W2605862165 cites W2143126277 @default.
• W2605862165 cites W2143298530 @default.
• W2605862165 cites W2143864965 @default.
• W2605862165 cites W2143977260 @default.
• W2605862165 cites W2144743578 @default.
• W2605862165 cites W2146366486 @default.
• W2605862165 cites W2148970839 @default.
• W2605862165 cites W2150861593 @default.
• W2605862165 cites W2155324027 @default.
• W2605862165 cites W2158238436 @default.
• W2605862165 cites W2158666214 @default.
• W2605862165 cites W2159295367 @default.
• W2605862165 cites W2160179097 @default.
• W2605862165 cites W2162383408 @default.
• W2605862165 cites W2162727140 @default.
• W2605862165 cites W2460916575 @default.
• W2605862165 doi "https://doi.org/10.1128/jvi.00253-17" @default.
• W2605862165 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5469260" @default.
• W2605862165 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28424286" @default.
• W2605862165 hasPublicationYear "2017" @default.
• W2605862165 type Work @default.
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• W2605862165 citedByCount "31" @default.

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