Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaoundé, Cameroon

Scientific Reports
Georges TetoGeorgette D Kanmogne

Abstract

In HIV-1 subtype-B, specific mutations in Gag cleavage sites (CS) are associated with treatment failure, with limited knowledge among non-B subtypes. We analyzed non-B HIV-1 gag and pol (protease/reverse-transcriptase) sequences from Cameroonians for drug resistance mutations (DRMs) in the gag P2/NC CS, and pol major DRMs. Phylogeny of the 141 sequences revealed a high genetic diversity (12 subtypes): 67.37% CRF02_AG versus 32.6% non-CRF02_AG. Overall, 7.3% transmitted and 34.3% acquired DRMs were found, including M184V, thymidine analogue mutations (T215F, D67N, K70R, K219Q), NNRTIs (L100I, Y181C, K103N, V108I, Y188L), and PIs (V82L). Twelve subjects [10 with HIV-1 CRF02_AG, 8 treatment-naïve and 4 on 3TC-AZT-NVP] showed 3 to 4 mutations in the Gag P2/NC CS: S373Q/T/A, A374T/S/G/N, T375S/A/N/G, I376V, G381S, and R380K. Subjects with or without Gag P2/NC CS mutations showed no significant difference in viral loads. Treatment-naïve subjects harboring NRTI-DRMs had significantly lower CD4 cells than those with NRTI-DRMs on ART (p = 0.042). Interestingly, two subjects had major DRMs to NRTIs, NNRTIs, and 4 mutations in the Gag P2/NC CS. In this prevailing CRF02_AG population with little exposure to PIs (~3%), mutations in the Gag ...Continue Reading

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Citations

Aug 17, 2019·Virology Journal·Lem Edith AbongwaFokunang Charles
Feb 19, 2020·Journal of the International Neuropsychological Society : JINS·Georgette D KanmogneRobert K Heaton
Dec 14, 2018·Scientific Reports·Georgette D KanmogneRobert K Heaton
Jul 14, 2021·Journal of Biomolecular Structure & Dynamics·Veronna Marie, Michelle Gordon
Sep 28, 2021·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Rufus O AkinyemiUNKNOWN African Dementia Consortium (AfDC)

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Datasets Mentioned

BETA
KX894018
KX894154

Methods Mentioned

BETA
ELISA
Fluorescence Activated Cell Sorting
FACS
PCR
electrophoresis
Genotyping

Software Mentioned

SCUEAL
CLUSTAL
MEGA
Rega
ClustalW
Bioedit
Pregap4
Splitstree
SimPlot
COMET

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