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Sexual Health Sexual Health Society
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RESEARCH ARTICLE

Cysteine 138 mutation in HIV-1 Nef from patients with delayed disease progression

Martin Tolstrup A B D , Alex L. Laursen A , Jan Gerstoft C , Finn S. Pedersen B , Lars Ostergaard A and Mogens Duch B

A Department of Infectious Diseases, Skejby Hospital, 8200 Aarhus, Denmark.

B Department of Molecular Biology, University of Aarhus, 8000 Aarhus, Denmark.

C Department of Epidemiology, Rigshospitalet, 2100 Copenhagen, Denmark.

D Corresponding author. Email: mt@mb.au.dk

Sexual Health 3(4) 281-286 https://doi.org/10.1071/SH06002
Submitted: 5 January 2006  Accepted: 10 April 2006   Published: 17 November 2006

Abstract

Background: The nef gene from HIV-1 has been shown to be an important pathogenic factor when considering development of AIDS. Detection of nef variants with an effect on immune modulation is important to understand HIV-1 pathogenesis and has possible impact on treatment strategies. Methods: The nef gene of HIV-1 isolates from patients in a long-term non-progressor (LTNP) cohort and a slow-progressor (SP) cohort (n = 11) was analysed and compared with isolates from a control patient group of progressors (n = 18). Most of the patients with delayed disease progression had extensive medical records, providing an insight into the LTNP disease profile and allowing for the stratification of patients based on their CD4 cell decline. Results: In sequences from nine patients, most of the functional domains of HIV-1 Nef appeared intact, and no major deletions were observed to possibly account for an effect on the delayed disease status. However, the results demonstrate a high incidence of a single amino acid polymorphism (cysteine 138) in HIV-1 Nef. The allelic frequency of cysteine 138 between the delayed disease progression group and the progressor group was found to be statistically significant (P = 0.0139). The phylogeny of isolates was investigated and the variants harbouring the cysteine 138 mutation clustered independently. Conclusion: The present study describes a viral genetic polymorphism related to AIDS disease progression. The polymorphism (cysteine 138) has previously been reported to confer decreased viral replication (Premkumar DR, et al. AIDS Res Hum Retroviruses 1996; 12(4): 337–45). A sequence database search for comparative mutations revealed a high frequency of cysteine 138 in patients with reported SP AIDS.


Acknowledgements

The authors’ wish to thank Jonna Guldberg for excellent technical assistance. MT is a scholar at the research school in Genetic Medicine. The project was supported by the Danish AIDS Foundation.


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