SARS-CoV-2 Infection Reactivates HIV-1 Replication From Latency in U1 Cells

Abstract

The global impact of COVID-19, caused by SARS-CoV-2, has infected millions, including those with HIV-1. However, it is unclear if SARS-CoV-2 affects HIV-1 reactivation from latency. Here, we used the U1 cell line to explore how SARS-CoV-2 infection affects HIV-1 reactivation from latency, employing real-time PCR assays and Western blot analysis. Our results show higher levels of HIV-1 RNA after SARS-CoV-2 infection. Importantly, we noticed enhanced reactivation of HIV-1 replication in cells infected with viruses carrying a deletion of amino acids R₆₈₂, R₆₈₃, A₆₈₄ (RRAΔ) in the spike (S) protein, compared to infections with viruses carrying the wild-type S protein. This is involvement of host transcription factors like NFAT, NF-κB p65, Ap-1, and Sp-1, which facilitate HIV production via TCR-related pathways. Additionally, activation of p-TEFb pathways enhances transcription elongation, upregulates Jak/Stat pathways, leading to increased viral replication, while TLR pathways impact the host immune response. Furthermore, RRAΔ showed increased apoptotic activity through both extrinsic and intrinsic apoptotic signaling pathways compared to wild-type SARS-CoV-2. These indicate that SARS-CoV-2 infection could revive HIV-1 replication from latency. The deletion of amino acids R₆₈₂R₆₈₃A₆₈₄ in the viral S protein might regulate further HIV-1 replication and apoptotic conditions, potentially benefiting HIV-1 survival.