Infection with dual-tropic human immunodeficiency virus type 1 variants associated with rapid total T cell decline and disease progression in injection drug users.
The characteristics of sequential human immunodeficiency virus type 1 (HIV-1) isolates from 12 seroconverters among injection drug users selected for either rapid or slow disease progression were evaluated. All 6 patients who developed AIDS within 5 years were initially infected with syncytium-inducing (SI) variants or showed a transition from non-SI-inducing (NSI) to SI variants. Detection of SI variants was associated with rapid decline of both CD8+ and CD4+ T cells. In contrast, the 6 slow progressors carried only NSI variants and maintained stable or increasing CD8+ T cell levels. The SI variants that were associated with initial infection were dual tropic, with efficient replication in primary macrophages and T cell lines. These results suggest that the ability to replicate in macrophages, rather than the SI or NSI phenotype per se, may be an important determinant of HIV-1 transmission and that dual-tropic viruses, when transmitted, may be associated with rapid progression to AIDS.
Yu
X F
XF
Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205, USA. xfyu@jhsph.edu
Wang
Z
Z
Vlahov
D
D
Markham
R B
RB
Farzadegan
H
H
Margolick
J B
JB
D000328:Adult; D000595:Amino Acid Sequence; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D006679:HIV Seropositivity / Q000150:complications* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015819:Substance Abuse, Intravenous / Q000150:complications*; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments