Neutral sphingomyelinase 2 is required for HIV-1 maturation.
Abdul A WaheedYanan ZhuEva AgostinoLwar NaingYuta HikichiFerri SoheilianSeung-Wan YooYun SongPeijun ZhangBarbara S SlusherNorman J HaugheyEric O FreedPublished in: Proceedings of the National Academy of Sciences of the United States of America (2023)
HIV-1 assembly occurs at the inner leaflet of the plasma membrane (PM) in highly ordered membrane microdomains. The size and stability of membrane microdomains is regulated by activity of the sphingomyelin hydrolase neutral sphingomyelinase 2 (nSMase2) that is localized primarily to the inner leaflet of the PM. In this study, we demonstrate that pharmacological inhibition or depletion of nSMase2 in HIV-1-producer cells results in a block in the processing of the major viral structural polyprotein Gag and the production of morphologically aberrant, immature HIV-1 particles with severely impaired infectivity. We find that disruption of nSMase2 also severely inhibits the maturation and infectivity of other primate lentiviruses HIV-2 and simian immunodeficiency virus, has a modest or no effect on nonprimate lentiviruses equine infectious anemia virus and feline immunodeficiency virus, and has no effect on the gammaretrovirus murine leukemia virus. These studies demonstrate a key role for nSMase2 in HIV-1 particle morphogenesis and maturation.
Keyphrases
- antiretroviral therapy
- hiv positive
- hiv infected
- hiv testing
- human immunodeficiency virus
- hepatitis c virus
- hiv aids
- men who have sex with men
- induced apoptosis
- heart failure
- sars cov
- oxidative stress
- chronic kidney disease
- mitral valve
- particulate matter
- acute myeloid leukemia
- air pollution
- aortic valve
- left ventricular
- atrial fibrillation
- cell death
- iron deficiency