Journal Article

HIV-1 and Its Strategy for Hiding Viral cDNA from STING-Mediated Innate Immunity

Gottikh, Marina, Mashkovskaia, Anna, Anisenko, Andrey, Oretskaya, Tatiana, Agapkina, Yulia

2025

Overview

Human immunodeficiency virus type 1 (HIV-1) is known to activate cytosolic DNA sensor pathways, such as the cGAS-STING pathway, the activation of which leads to interferon production. The primary source of this activation is reverse transcription of the viral RNA genome into cDNA, which occurs in the cytoplasm. However, the degree of cytosolic DNA sensor activation during HIV-1 infection is significantly lower compared to that induced by DNA-containing viruses or even by the related HIV-2. This can be attributed to the successful evasion of innate immune recognition pathways by HIV-1, particularly through the disruption of cGAS-STING signaling pathway activation. In this review, we summarize the available information regarding the mechanisms employed by HIV-1 to conceal viral cDNA from cytosolic DNA sensors. Deciphering these mechanisms may reveal potential vulnerabilities that could be targeted to develop novel antiviral approaches.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: Animals / Cytoplasm / Dendritic cells / DNA, Complementary - genetics / DNA, Complementary - immunology / DNA, Viral - genetics / DNA, Viral - immunology / Gene expression / Genetic engineering / Genomes / HIV / HIV Infections - immunology / HIV Infections - metabolism / HIV Infections - virology / HIV-1 - genetics / HIV-1 - immunology / Human immunodeficiency virus / Humans / Immune system / Immunity (Disease) / Immunity, Innate / Infections / Interferon / Kinases / Membrane Proteins - immunology / Membrane Proteins - metabolism / Nucleotidyltransferases - metabolism / Polymorphism / Review / Sensors / Signal Transduction / Viruses