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Updated: Jul 24, 2025
07:10
Humanized NOD/SCID/IL2rγnull (hu-NSG) Mouse Model for HIV Replication and Latency Studies
Published on: January 7, 2019
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Neutral sphingomyelinase 2 is required for HIV-1 maturation
Abdul A Waheed1, Yanan Zhu2, Eva Agostino1
1Virus-Cell Interaction Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.
Summary
Neutral sphingomyelinase 2 (nSMase2) is crucial for human immunodeficiency virus type 1 (HIV-1) assembly and maturation. Inhibiting nSMase2 blocks Gag processing, yielding immature, non-infectious viral particles.
Area of Science:
- Virology
- Cell Biology
- Biochemistry
Background:
- Human immunodeficiency virus type 1 (HIV-1) assembly is linked to plasma membrane microdomains.
- Neutral sphingomyelinase 2 (nSMase2) regulates membrane microdomain structure and stability.
- nSMase2 is localized to the inner leaflet of the plasma membrane.
Purpose of the Study:
- To investigate the role of nSMase2 in HIV-1 particle morphogenesis and maturation.
- To determine the effect of nSMase2 inhibition on HIV-1 Gag processing and infectivity.
Main Methods:
- Pharmacological inhibition and genetic depletion of nSMase2 in HIV-1-producing cells.
- Analysis of viral particle morphology, Gag polyprotein processing, and infectivity.
- Comparative studies across different lentiviruses and retroviruses.
Main Results:
- nSMase2 inhibition blocked Gag processing, leading to immature HIV-1 particles.
- Inhibited HIV-1 particles exhibited aberrant morphology and severely impaired infectivity.
- nSMase2 disruption affected primate lentiviruses (HIV-2, SIV) but not non-primate lentiviruses or gammaretroviruses.
Conclusions:
- nSMase2 plays a critical role in HIV-1 particle morphogenesis and maturation.
- nSMase2's function in lentiviral replication is specific to primate lentiviruses.
- Targeting nSMase2 could be a strategy for developing novel anti-HIV therapies.
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