Global Variability of V3 Loop Tetrapeptide Motif: a Concern for HIV-1 Neutralizing Antibodies-based Vaccine Design and Antiretroviral Therapy

Lopes, Luciano Rodrigo; Silva, Antonio Carlos da; Bandiera-Paiva, Paulo; Casseb, Jorge

doi:10.52547/jommid.9.3.108

Cited by 1 publication

(4 citation statements)

References 53 publications

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“…It has also shown a reduced viral load among female patients and elevated CD4+ T cell counts in this population 8 . The GWGR motif increases the binding avidity of neutralizing antibodies 31 and does not confer antiretroviral resistance 18 . These findings may contribute to the reported milder pathogenic potential previously observed 33 .…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, GPGQ or GPGK motifs favor elevating the pathogenic potential of the HIV-1 strains. For instance, both motifs can reduce the binding capacity of neutralizing antibodies 18 . The higher pathogenic potential of the non-GWGR strains may have contributed to anticipating the HIV-1 disease progression, found by this study.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the relative degree of conservation of GPGR, this motif presents substantial variability due to the need to maintain the functional role of the V3 loop. Besides GPGR, found in the HIV-1 reference strain, the GPGQ and GPGK motifs are massively found in HIV-1 strains 18 .…”

Section: Introductionmentioning

confidence: 98%

“…Additionally, the GWGR motif promotes or is correlated with a higher affinity for neutralizing antibodies produced against the V3 region, contributing to a slower disease progression 30 , 31 . On the other hand, HIV-1 strains with GPGR, GPGQ, and GPGK motifs in their V3 crown can escape from neutralizing antibodies 32 and resist fusion inhibitor drugs, conferring the most pathogenic clinical course 18 .…”

Section: Introductionmentioning

confidence: 99%

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Unraveling clinical outcomes of long-term cART treatment in HIV-1 patients with or without the Brazilian GWGR motif in the V3 loop

Folgosi,

Komninakis,

Lopes

et al. 2024

Rev. Inst. Med. trop. S. Paulo

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The presence of genetic mutations in HIV poses a significant challenge, potentially leading to antiretroviral resistance and hampering therapeutic development. The Brazilian population has presented variations in the HIV envelope V3 loop gene, especially the GWGR motif. This motif has been linked to reduced transmission potential and slower CD4+ T cell decline. This study aimed to assess clinical outcomes in patients with HIV-1 infected with strains containing the GWGR motif compared with those without it during long-term cART. A cohort of 295 patients with HIV was examined for the GWGR motif presence in the V3 loop. A total of 58 samples showed the GWGR signature, while 237 had other signatures. Multifactorial analyses showed no significant differences in demographic characteristics, CD4+ cell count, AIDS progression, or mortality between GWGR carriers and others. However, the mean interval between the first positive HIV test and the initial AIDS-defining event was more than two times longer for women carrying the GWGR signature (p = 0.0231). We emphasize the positive impact of cART on HIV/AIDS treatment, including viral suppression, CD4+ cell preservation, and immune function maintenance. Although no significant differences were found during cART, residual outcomes reflecting adherence challenges were observed between diagnosis and the first AIDS-defining event. The previously described outcomes, highlighting statistically significant differences between individuals carrying the GPGR motif compared with those with the Brazilian GWGR motif, may be directly linked to the natural progression of infection before advancements in cART. Presently, these physicochemical aspects may no longer hold the same relevance.

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