NDLI: Coreceptor Phenotype of Natural Human Immunodeficiency Virus with Nef Deleted Evolves In Vivo, Leading to Increased Virulence

Content Provider	PubMed Central
Author	Andreas, Jekle Schramm, Birgit Jayakumar, Prerana Trautner, Verena Schols, Dominique Clercq, Erik De Mills, John Crowe, Suzanne M. Goldsmith, Mark A.
Copyright Year	2002
Abstract	The Sydney Blood Bank Cohort is a group of patients with slowly progressive infection by a human immunodeficiency virus strain containing spontaneous deletions within the nef long terminal repeat region. In 1999, 18 years after the initial infection, one of the members (D36) developed AIDS. In this work, we used an ex vivo human lymphoid cell culture system to analyze two viral isolates obtained from this patient, one prior to the onset of AIDS in 1995 and one after disease progression in 1999. Both D36 isolates were less potent in depleting CD4+ T cells than a reference dualtropic, nef-bearing viral isolate. However, the 1999 isolate was measurably more cytotoxic to CD4+ T cells than the 1995 isolate. Interestingly, although both isolates were nearly equally potent in depleting CCR5+ CD4+ T cells, the cytotoxic effect of the 1999 isolate toward CCR5− CD4+ T cells was significantly higher. Furthermore, GHOST cell infection assays and blocking experiments with the CXCR4 inhibitor AMD3100 showed that the later D36 1999 isolate could infect both CCR5+ and CCR5− CXCR4+ cells efficiently, while infection by the 1995 isolate was nearly completely restricted to CCR5+ cells. Sequence analysis of the V1/V2 and V3 regions of the viral envelope protein gp120 revealed that the more efficient CXCR4 usage of the later isolate might be caused by an additional potential N-glycosylation site in the V1/V2 loop. In conclusion, these data show that an in vivo evolution of the tropism of this nef-deleted strain toward an X4 phenotype was associated with a higher cytopathic potential and progression to AIDS.
Related Links	http://dx.doi.org/10.1128/JVI.76.14.6966-6973.2002
Starting Page	6966
File Format	PDF
ISSN	10985514
e-ISSN	10985514
Journal	Journal of Virology
Issue Number	14
Volume Number	76
Language	English
Publisher	American Society for Microbiology
Publisher Date	2002-07-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Virology Immunology Microbiology Insect Science

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