Abstract
The HIV envelope protein contains five hypervariable domains (V1-V5) that are fundamental for cell entry. We contrasted modifications in the variable domains derived from a panel of 24 tissues from 7 subjects with no measurable plasma viral load (NPVL) to variable domains from 76 tissues from 15 subjects who had a detectable plasma viral load (PVL) at death. NPVL subject's V1 and V2 domains were usually highly length variable, whereas length variation in PVL sequences was more conserved. Longer V1s contained more charged residues, whereas longer V2s were more glycosylated. Structural analysis demonstrated V1/V2 charge, and N-site additions/subtractions were localized to the CD4 binding pocket. Diversified envelopes in tissues during therapy may represent a mechanism for HIV persistence in tissues, as binding pocket complexity is associated with HIV that may escape neutralization, whereas shorter envelopes are associated with increased infectivity. Further analysis of tissue-derived envelope sequences may enable better understanding of potential immunological approaches targeting the persistent HIV reservoir.
References
Sep 5, 2001·Neuropathology and Applied Neurobiology·S MorgelloE J Singer
Apr 29, 2005·Journal of Virology·Simon D W FrostDouglas D Richman
Apr 29, 2005·Journal of Virology·Bhavna ChohanJulie Overbaugh
Jan 25, 2008·BMC Bioinformatics·Yang Zhang
Apr 1, 2009·PloS One·Susanna L LamersMichael S McGrath
Jun 3, 2009·The Journal of Experimental Medicine·Jesus F Salazar-GonzalezGeorge M Shaw
Apr 3, 2010·Nature Protocols·Ambrish RoyYang Zhang
Oct 16, 2010·Methods in Molecular Biology·Leona W AyersDebra L Garcia
Oct 8, 2011·PLoS Pathogens·S GnanakaranBette Korber
Nov 25, 2011·Nature·Jason S McLellanPeter D Kwong
Oct 23, 2012·Nature Medicine·Penny L MooreLynn Morris
Jul 29, 2016·Journal of Virology·Susanna L LamersElyse J Singer
Sep 22, 2016·Sarcoma·Susanna L LamersMichael S McGrath
Jul 13, 2017·Nature·Gabriel OzorowskiAndrew B Ward
Aug 5, 2017·Journal of Virology·Maria Paz Gonzalez-PerezPaul R Clapham
Nov 1, 2017·AIDS Research and Human Retroviruses·David J NolanMichael S McGrath
Apr 25, 2018·Journal of Neurovirology·Robin L BreseSusanna L Lamers