Novel mechanism of HIV elite control by enriching gut dipeptides as HIV-1 antagonist but Prevotella agonist

Abstract

HIV-1 Elite controllers (EC) are a rare group among HIV-1-infected individuals who can naturally control viral replication for a prolonged period. Due to their heterogeneous nature, no universal mechanism could be attributed to the EC status; instead, several host and viral factors are discussed for playing a role. In this study, we investigated the fecal metabolome and microbiome in a Swedish cohort of EC, treatment-naïve viremic progressors (VP) and HIV-negative individuals (HC). We observed an enrichment of dipeptides in EC compared to the other two study groups. In vitro analyses identified anti-HIV-1 properties for two dipeptides that could bind to the HIV-1 gp120. Furthermore, these dipeptides supported bacterial growth of the genus Prevotella in vitro that was enriched in EC, which influences host metabolism. Thus, increased levels of both dipeptides and Prevotella could provide beneficial effects for EC. These findings open new possibilities to develop therapeutics against HIV-1.

Broad synergistic antiviral efficacy between a novel elite controller-derived dipeptide and antiretrovirals against drug-resistant HIV-1

“…The dipeptide WG-am emerged as notably elevated in elite controllers (ECs) in comparison to viral progressors (VPs) and healthy controls (HCs). We have demonstrated the low toxicity of WG-am both in isolation and in combination with other compounds (Sperk et al, 2021;Cena-Diez et al, 2022). Building on these findings, we have shown that it has anti-HIV-1 activity (Sperk et al, 2021;Cena-Diez et al, 2023a).…”

“…We have demonstrated the low toxicity of WG-am both in isolation and in combination with other compounds (Sperk et al, 2021;Cena-Diez et al, 2022). Building on these findings, we have shown that it has anti-HIV-1 activity (Sperk et al, 2021;Cena-Diez et al, 2023a). WG-am binds to the CD4 binding pocket of HIV-1 gp120 blocking the interaction between the virus and the CD4 receptor and also inhibits HIV-1 reverse transcription (Cena-Diez et al, 2023a).…”

An overview of “Chronic viral infection and cancer, openings for vaccines” virtual symposium of the TechVac Network - December 16-17, 2021

“…Furthermore, these dipeptides supported in vitro growth of the bacterial genus Prevotella enriched in EC, pinpointing its influence on the host metabolism. Thus, increased levels of both dipeptides and Prevotella could provide beneficial effects for EC [21]. Given that EC is a rare group of individuals, people living with HIV (PLWH) with longterm treatment were also analyzed.…”

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“…The dipeptide WG-am emerged as notably elevated in elite controllers (ECs) in comparison to viral progressors (VPs) and healthy controls (HCs). We have demonstrated the low toxicity of WG-am both in isolation and in combination with other compounds (Sperk et al, 2021;Cena-Diez et al, 2022). Building on these findings, we have shown that it has anti-HIV-1 activity (Sperk et al, 2021;Cena-Diez et al, 2023a).…”

“…We have demonstrated the low toxicity of WG-am both in isolation and in combination with other compounds (Sperk et al, 2021;Cena-Diez et al, 2022). Building on these findings, we have shown that it has anti-HIV-1 activity (Sperk et al, 2021;Cena-Diez et al, 2023a). WG-am binds to the CD4 binding pocket of HIV-1 gp120 blocking the interaction between the virus and the CD4 receptor and also inhibits HIV-1 reverse transcription (Cena-Diez et al, 2023a).…”