Greater Diversity of HIV-1 Quasispecies in HIV-Infected Individuals With Active Tuberculosis
作者:
Kalonji Collins,
Harriet Mayanja-Kizza,
Barbara Sullivan,
Miguel Quiñones-Mateu,
Zahra Toossi,
Eric Arts,
期刊:
JAIDS Journal of Acquired Immune Deficiency Syndromes
(OVID Available online 2000)
卷期:
Volume 24,
issue 5
页码: 408-417
ISSN:1525-4135
年代: 2000
出版商: OVID
关键词: HIV;AIDS;Heterogeneity;Tuberculosis
数据来源: OVID
摘要:
ObjectiveA continual increase in intrapatient HIV-1 heterogeneity is thought to contribute to evasion of host immune response and eventual progression to AIDS. Tuberculosis (TB) is diagnosed both early and late during the course of HIV-1 disease and may increase diversity of HIV-1 quasispecies by activating the HIV-1 immune response and increasing HIV-1 replication. We examined whether HIV-1 heterogeneity is altered in HIV-1–infected individuals with TB.MethodsBlood samples were obtained from 7 HIV-1–infected patients with active TB (HIV/TB patients) and 9 HIV-1–infected patients (HIV patients) in Kampala, Uganda (CD4 counts of 0–650 cells/&mgr;l and HIV loads of 700–750,000 RNA copies/ml). The C2-C3 region of the HIV-1 envelope gene (env) was amplified by nested polymerase chain reaction (PCR) from lysed peripheral blood mononuclear cells (PBMCs) of each patient, and then subject to sequencing, clonal-quasispecies analysis and heteroduplex tracking analysis (HTA).ResultsHTA ofenvDNA fragments showed increased heterogeneity in the HIV/TB individuals compared with the HIV group. Further sequence and HTA analysis on ten individualenvclones for each patient showed significantly greater HIV mutation frequencies in HIV/TB patients than in HIV patients.ConclusionAn increase in HIV-1 heterogeneity may be associated with a TB-mediated increase in HIV-1 replication. However, a diverse HIV-1 quasispecies population in HIV/TB patients as opposed to tight quasispecies clusters in HIV patients suggests a possible dissemination of lung-derived HIV-1 isolates from the TB-affected organ.
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