Characterization of envelope sequence of HIV virus in children infected with HIV in Vietnam

Abstract

Background: HIV is characterized by high levels of genetic variability, including increased numbers of heterogeneous sequences of the envelope region. Therefore, studying genetic variability of HIV in relation to viral replication might facilitate prognosis of disease progression. Methods: The study was designed as cross-sectional; data and samples of participants collected and analyzed env genes were obtained from 23 children enrolled by Vietnam National Children’s Hospital. Results: Substantial mutations in the C2 region were found in patients with high levels of viral replication while changes in the C3 region were mostly found in patients with low viral load. In the V1 region, we found profound amino acid modifications in patients with low HIV viral loads in contrast to the V2 sequence, where we identified single point mutations in patients with increased HIV viral load. The V3 region was relatively homogeneous, while profound deletions in the V4 region were detected in patients with increased viral replication. Conclusion: Our results suggest that genetic variations in different regions of the HIV envelope sequence, including both conserved C2 and C3 and variable V1/V2 and V4 regions, might be involved in increased viral infectivity and replication capacity. Such knowledge might help improve prediction of HIV progress and treatment in patients.

The Characteristics of the HIV-1 Env Glycoprotein Are Linked With Viral Pathogenesis

“…The growth in functionality of the viral characteristics was also correlated with the genetic distance of the sequences to the subtype B ancestor. Genetic variability in the env gene has been associated with an increase in viral infectivity and replication capacity ( Keele et al, 2008 ; Quan et al, 2009 ; Fischer et al, 2010 ; Roche et al, 2011 ; Fraser et al, 2014 ; Dang et al, 2020 ). These changes could facilitate viral replication by increasing viral fitness that favors the escape from the immune response and ART ( Koot et al, 1993 ; Kitrinos et al, 2003 , 2005 ; Kitchen et al, 2004 ; Hunt et al, 2006 ; Duenas-Decamp et al, 2008 ; Salazar-Gonzalez et al, 2008 ; Kassaye et al, 2009 ; Moore et al, 2009 ; Shi et al, 2010 ).…”

Contribution of the HIV-1 Envelope Glycoprotein to AIDS Pathogenesis and Clinical Progression

“…It is conceivable that better HIV-1 Env functions could promote viral fitness and would therefore favour resistance against the immune response [ 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 , 209 ]. It is noteworthy that HIV-1 env variability has also been related with better viral infectivity and replication capacities [ 184 , 185 , 186 , 187 , 188 , 189 ]. A last example was reported in a LTNP-EC who discontinued ART [ 210 ].…”

“…During viral transmission to a new host, a selection for viral variants with shorter variable regions and a reduced degree of PNGs occurs in viruses from the HIV-1 subtype B [ 183 ]. An increase in viral infectivity and replication capacity has been associated with genetic variability in the env gene [ 184 , 185 , 186 , 187 , 188 , 189 ]. This viral replication could favor the gain of function of the HIV-1 env by increasing viral fitness and could result in the escape from the immune response and ART [ 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 ].…”

Potential Associations of Mutations within the HIV-1 Env and Gag Genes Conferring Protease Inhibitor (PI) Drug Resistance

“…These were mostly in the variable loops (V2: D167AR, V182I, P183QS, Y191F and N195H, and V3: S306R, P313DI, Q315R, I323KNR, A329DT, and C331RS); however, increased frequencies were also observed in the constant regions (C2: N230DT, Q258EP, N262LI, T283I, V286I and I294N, and C3: W338EG, H374KR, F382V, and F383LV). Amino acid changes in these regions can, therefore, potentially increase the infectivity and replication capacity of the virus [33].…”