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.
Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205, USA. xfyu@jhsph.edu
X F
XF
Yu
Z
Z
Wang
D
D
Vlahov
R B
RB
Markham
H
H
Farzadegan
J B
JB
Margolick
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