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The nef gene from a long-term HIV type 1 nonprogressor
D R Premkumar1, X Z Ma, R K Maitra
1Department of Molecular Biology, Research Institute, The Cleveland Clinic Foundation, Ohio 44195, USA.
AIDS Research and Human Retroviruses
|March 1, 1996
Summary
A specific mutation in the nef gene (cysteine at amino acid 138) of human immunodeficiency virus type 1 (HIV-1) may indicate an attenuated virus. This finding offers insights into HIV-1 attenuation and potential therapeutic targets.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- The nef gene of human immunodeficiency virus type 1 (HIV-1) is crucial for AIDS pathogenesis.
- Simian immunodeficiency virus (SIV) lacking nef is infectious but cannot induce high viral loads or AIDS in rhesus monkeys.
Observation:
- A long-term nonprogressor harbored HIV-1 (Sur25) with an open nef gene, but with a consistent cysteine mutation at amino acid 138.
- This Cys-138 mutation was also found in nef genes of other asymptomatic individuals and in related lentiviruses like chimpanzee immunodeficiency virus (CIV) and SIVagm, which do not cause AIDS.
Findings:
- The Cys-138 mutation in HIV-1 nef appears to be associated with attenuated viral properties, similar to nef-deleted SIVmac and HIV.
- Nef protein with Cys-138 specifically determines the virus's ability to grow in H9 cells, suggesting a role in viral replication capacity.
Implications:
- The Cys-138 mutation may serve as a marker for attenuated HIV-1 strains.
- Understanding the role of this mutation could lead to strategies for developing less pathogenic lentiviruses or novel therapeutic interventions for HIV/AIDS.