DOI: 10.1073/pnas.142313699. Evidence for a cytopathogenicity determinant in HIV-1 Vpr

Evidence for a cytopathogenicity determinant in HIV-1 Vpr

10.1073/pnas.142313699

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

HIV-1 is cytopathic for CD4+T lymphocytesin vitroand this property of HIV-1 is generally considered to account for some of itsin vivocytopathogenicity. Thus, the extent of lymphocyte depletion correlates with the level of viremia whereas low levels of viral replication are typically associated with stable lymphocyte levels and asymptomatic infection such as is observed in non-progressors. Here, we describe a non-progressor who did not fit this general pattern in that CD4+T lymphocyte homeostasis was maintained in the face of high-level viral replication. Biological viral isolates from this patient replicated in primary lymphocytes without inducing cytopathicity. Because this phenotype is reminiscent of Vpr-deleted viruses, we examined the contribution of the Vpr gene to the viral phenotype. Vpr alleles derived from this patient contained both premature stop codons and an unusual Q3R polymorphism. Insertion of patient-derived Vpr alleles or a Q3R substitution into a cytopathic HIV-1 clone resulted in a marked impairment of cytopathicity without affecting viral replication efficiency. The effect of Vpr on cytopathicity was unrelated to reported activities of Vpr including virion association, interaction with uracil DNA glycosylase, G2arrest, or enhancement of macrophage infection but correlated with the ability of Vpr to induce host cell apoptosis. This study suggests the presence of a determinant ofin vivocytopathogenicity within HIV-1 Vpr and further indicates that viral replication can be uncoupled from cytopathicityin vitroandin vivo.

Bibliography

Somasundaran, M., Sharkey, M., Brichacek, B., Luzuriaga, K., Emerman, M., Sullivan, J. L., & Stevenson, M. (2002). Evidence for a cytopathogenicity determinant in HIV-1 Vpr. Proceedings of the National Academy of Sciences, 99(14), 9503â9508.

Authors 7

Mohan Somasundaran (first)
Mark Sharkey (additional)
Beda Brichacek (additional)
Katherine Luzuriaga (additional)
Michael Emerman (additional)
John L. Sullivan (additional)
Mario Stevenson (additional)

References 34 Referenced 86

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Dates

Type	When
Created	23 years, 1 month ago (July 28, 2002, 6:26 p.m.)
Deposited	2 years, 4 months ago (April 23, 2023, 7:40 p.m.)
Indexed	6 days, 9 hours ago (Aug. 30, 2025, 12:26 p.m.)
Issued	23 years, 2 months ago (July 1, 2002)
Published	23 years, 2 months ago (July 1, 2002)
Published Online	23 years, 2 months ago (July 1, 2002)
Published Print	23 years, 1 month ago (July 9, 2002)

Funders 0

None

BibTeX

@article{Somasundaran_2002, title={Evidence for a cytopathogenicity determinant in HIV-1 Vpr}, volume={99}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.142313699}, DOI={10.1073/pnas.142313699}, number={14}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Somasundaran, Mohan and Sharkey, Mark and Brichacek, Beda and Luzuriaga, Katherine and Emerman, Michael and Sullivan, John L. and Stevenson, Mario}, year={2002}, month=jul, pages={9503–9508} }

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