[How do 2'-O-methylations within Human Immunodeficiency Virus type 1 (HIV-1) genome regulate its replication?]
Alice DecombePriscila El-KazziSébastien NisoleÉtienne DecrolyPublished in: Medecine sciences : M/S (2024)
The genomic RNA of HIV-1 is modified by epitranscriptomic modifications, including 2'-O-methylations, which are found on 17 internal positions. These methylations are added by the cellular methyltransferase FTSJ3, and have pro-viral effects, since they shield the viral genome from the detection by the innate immune sensor MDA5. In turn, the production of interferons by infected cells is reduced, limiting the expression of interferon-stimulated genes (ISGs) with antiviral activities. Moreover, 2'-O-methylations protect the HIV-1 genome from its degradation by ISG20, an interferon-induced exonuclease. Conversely, these methylations also exhibit antiviral effects, as they impede reverse-transcription in vitro or in quiescent cells, which are known to contain low nucleotide concentrations. Altogether, these observations suggest a balance between the proviral effect of 2'-O-methylations, related to the protection of the viral genome from detection by MDA5 and degradation by ISG20, and the antiviral effect, associated with the negative impact of 2'-O-methylations on the viral replication. These findings pave the way for further optimization of therapeutic RNA, by selective methylation of specific nucleotides.
Keyphrases
- human immunodeficiency virus
- antiretroviral therapy
- hepatitis c virus
- hiv infected
- genome wide
- hiv positive
- cell cycle arrest
- sars cov
- induced apoptosis
- hiv aids
- hiv testing
- innate immune
- cell death
- dna methylation
- breast cancer cells
- poor prognosis
- south africa
- drug induced
- copy number
- oxidative stress
- loop mediated isothermal amplification
- pi k akt
- high glucose
- transcription factor
- anti inflammatory