Greater diversity of HIV-1 quasispecies in HIV-infected individuals with active tuberculosis.
OBJECTIVE
A 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.


METHODS
Blood 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/microl 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).


RESULTS
HTA of env DNA fragments showed increased heterogeneity in the HIV/TB individuals compared with the HIV group. Further sequence and HTA analysis on ten individual env clones for each patient showed significantly greater HIV mutation frequencies in HIV/TB patients than in HIV patients.


CONCLUSIONS
An 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.
Collins
K R
KR
Division of Infectious Diseases, Department of Medicine, and Molecular Virology Training Program, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Mayanja-Kizza
H
H
Sullivan
B A
BA
Quiñones-Mateu
M E
ME
Toossi
Z
Z
Arts
E J
EJ
D000328:Adult; D001483:Base Sequence; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000097:blood / Q000737:chemistry; D005260:Female; D014644:Genetic Variation; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics; D020180:Heteroduplex Analysis; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014397:Tuberculosis, Pulmonary / Q000150:complications*; D014454:Uganda / Q000453:epidemiology
D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments