V5 region in the HIV-1 envelope glycoprotein determines viral sensitivity to the broadly neutralizing monoclonal antibody VRC01

Guo, Deyin; Shi, Xuanling; Arledge, Kelly C.; Song, Dingka; Jiang, Liwei; Fu, Lili; Zhang, S; X, Wang; Zhang, L

doi:10.1186/1742-4690-9-s2-p46

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A contradictory trend was observed for V5 region amino acid length and viral load. This observation is complimenting recent findings which have demonstrated that increased sequence length and glycosylation in in the V5 region may collectively create steric hindrance that lowers binding affinity, thereby increasing resistance to neutralization [31]. A subtype C study of a single Zambian HIV infected but slowly progressing infant showed that neither lengthening of the V1V5 domain nor the acquisition of glycosylation site were not always a component glycoprotein evolution in newly infected children [20].…”

Section: Discussionsupporting

confidence: 77%

HIV-1 subtype C envelope C2V5 characteristics; associations with markers of disease progression among 6 slowing progressing pediatric patients

Duri¹,

Gumbo²,

Kristiansen³

et al. 2013

Virol Discov

View full text Add to dashboard Cite

Background: HIV-1 gp120 envelope variable regions potential N-glycosylation sites (PNGs) and amino acid length polymorphisms have been shown to play pivotal roles in disease progression in spite of other studies demonstrating contradictory results. Methods: Regression analysis was used to assess the association between changes in PNGs or amino acid sequence lengths of C2V5 region/sub-regions and disease progression as a function of HIV-1 RNA load or CD4% among antiretroviral therapy naïve subtype C infected but slowly disease progressing children. Results: Unit increases in amino acid sequence lengths within the V3 region was associated with a 5 unit increase in CD4%, p=0.010. Unit increases in PNGs within the C2V5 region, V3 and V5 sub-regions were associated with 3, 9 and 8 unit increases in CD4%; p=0.041, 0.040 and 0.02, respectively. Interestingly, a unit PNGs increase within the C4 sub-region correlated with a 1.2 million copies/ml decrease in viral load, p=0.009. Conclusion: C4 sub-region PNGs may be influential in viral replications whilst amino acid length polymorphism within the V3 regions could be key in host immunological surveillance. However, bigger studies with more clones per sample are warranted to substantiate these preliminary findings and whether such observations are also true for the adult the population.

show abstract

Section: Discussionsupporting

confidence: 77%

HIV-1 subtype C envelope C2V5 characteristics; associations with markers of disease progression among 6 slowing progressing pediatric patients

Duri¹,

Gumbo²,

Kristiansen³

et al. 2013

Virol Discov

View full text Add to dashboard Cite

show abstract

“…In this study we saw an increase in the number of N-glycosylation sites in the V1/V2 region, increased sequence variation in V1/V2 and V5, as well as an increased V1/V2 loop length in the treated group vs. naïve group. Taken together, since these types of changes have previously been shown to protect the virus against neutralization by reducing antibody binding affinity through steric hindrance, this suggests that evasion of the host immune system is also one of the mechanisms used by the virus during the development of drug resistance (Pollakis et al, 2001;van Gils et al, 2011;Guo et al, 2012;Wang et al, 2013). Specifically, the length of the V2 and V5 regions seen in our naïve group (34-41 amino acids and 10-12 amino acid respectively) were similar to those reported by Mandizvo et al (2022) for untreated HIV-1 subptype C (34-48 and 10-13 respectively) (Mandizvo et al, 2022), which strongly supports that the increased V2 and V5 length (41-55 and 10-16 respectively) in our treated group could be related to treatment.…”

Section: Discussionmentioning

confidence: 99%

HIV-1 envelope facilitates the development of protease inhibitor resistance through acquiring mutations associated with viral entry and immune escape

Maphumulo,

Gordon

2024

Front. Microbiol.

View full text Add to dashboard Cite

IntroductionThere is increasing evidence supporting a role for HIV-1 envelope in the development of Protease Inhibitor drug resistance, and a recent report from our group suggested that Env mutations co-evolve with Gag-Protease mutations in the pathway to Lopinavir resistance. In this study, we investigated the effect of co-evolving Env mutations on virus function and structure.MethodsCo-receptor usage and n-linked glycosylation were investigated using Geno2Pheno as well as tools available at the Los Alamos sequence database. Molecular dynamics simulations were performed using Amber 18 and analyzed using Cpptraj, and molecular interactions were calculated using the Ring server.ResultsThe results showed that under Protease Inhibitor drug selection pressure, the envelope gene modulates viral entry by protecting the virus from antibody recognition through the increased length and number of N-glycosylation sites observed in V1/V2 and to some extent V5. Furthermore, gp120 mutations appear to modulate viral entry through a switch to the CXCR4 coreceptor, induced by higher charge in the V3 region and specific mutations at the coreceptor binding sites. In gp41, S534A formed a hydrogen bond with L602 found in the disulfide loop region between the Heptad Repeat 1 and Heptad Repeat 2 domains and could negatively affect the association of gp120-gp41 during viral entry. Lastly, P724Q/S formed both intermolecular and intramolecular interactions with residues within the Kennedy loop, a known epitope.DiscussionIn conclusion, the results suggest that mutations in envelope during Protease Inhibitor treatment failure are related to immune escape and that S534A mutants could preferentially use the cell-to-cell route of infection.

show abstract

V5 region in the HIV-1 envelope glycoprotein determines viral sensitivity to the broadly neutralizing monoclonal antibody VRC01

Cited by 2 publications

References 0 publications

HIV-1 subtype C envelope C2V5 characteristics; associations with markers of disease progression among 6 slowing progressing pediatric patients

HIV-1 subtype C envelope C2V5 characteristics; associations with markers of disease progression among 6 slowing progressing pediatric patients

HIV-1 envelope facilitates the development of protease inhibitor resistance through acquiring mutations associated with viral entry and immune escape

Contact Info

Product

Resources

About