HIV-2 inhibits HIV-1 gene expression via two independent mechanisms during cellular co-infection.
Vincent YapoKinjal MajumderPhilip R TedburyXin WenYee T OngMarc C JohnsonStefan G SarafianosPublished in: Journal of virology (2023)
Twenty-five years after the first report that HIV-2 infection can reduce HIV-1-associated pathogenesis in dual-infected patients, the mechanisms are still not well understood. We explored these mechanisms in cell culture and showed first that these viruses can co-infect individual cells. Under specific conditions, HIV-2 inhibits HIV-1 through two distinct mechanisms, a broad-spectrum interferon response and an HIV-1-specific inhibition conferred by the HIV-2 TAR. The former could play a prominent role in dually infected individuals, whereas the latter targets HIV-1 promoter activity through competition for HIV-1 Tat binding when the same target cell is dually infected. That mechanism suppresses HIV-1 transcription by stalling RNA polymerase II complexes at the promoter through a minimal inhibitory region within the HIV-2 TAR. This work delineates the sequence of appearance and the modus operandi of each mechanism.
Keyphrases
- antiretroviral therapy
- hiv positive
- hiv infected
- hiv testing
- human immunodeficiency virus
- hiv aids
- hepatitis c virus
- men who have sex with men
- gene expression
- south africa
- dna methylation
- transcription factor
- stem cells
- immune response
- signaling pathway
- single cell
- oxidative stress
- mesenchymal stem cells
- induced apoptosis
- bone marrow
- cell therapy
- dna binding