Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population.
The composition of human immunodeficiency virus type 1 (HIV-1) clonal populations at different stages of infection and in different compartments was analyzed. Biological HIV-1 clones were obtained by primary isolation from patient peripheral blood mononuclear cells under limiting dilution conditions, with either blood donor peripheral blood lymphocytes or monocyte-derived macrophages (MDM) as target cells, and the biological phenotype of the clones was analyzed. In asymptomatic individuals, low frequencies of HIV-1 clones were observed. These clones were non-syncytium inducing and preferentially monocytotropic. In individuals progressing to disease, a 100-fold increase in frequencies of productively HIV-1-infected cells was observed as a result of a selective expansion of nonmonocytotropic clones. In a person progressing to AIDS within 19 months after infection, only syncytium-inducing clones were detected, shifting from MDM-tropic to non-MDM-tropic over time. From his virus donor, a patient with wasting syndrome, only syncytium-inducing clones, mostly non-MDM-tropic, were recovered. Parallel clonal analysis of HIV-1 populations in cells present in bronchoalveolar lavage fluid and peripheral blood from an AIDS patient revealed a qualitatively and quantitatively more monocytotropic virus population in the lung compartment than in peripheral blood at the same time point. These findings indicate that monocytotropic HIV-1 clones, probably generated in the tissues, are responsible for the persistence of HIV-1 infection and that progression of HIV-1 infection is associated with a selective increase of T-cell-tropic, nonmonocytotropic HIV-1 variants in peripheral blood.
Schuitemaker
H
H
Central Laboratory, Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Koot
M
M
Kootstra
N A
NA
Dercksen
M W
MW
de Goede
R E
RE
van Steenwijk
R P
RP
Lange
J M
JM
Schattenkerk
J K
JK
Miedema
F
F
Tersmette
M
M
D000163:Acquired Immunodeficiency Syndrome / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000473:pathology; D015658:HIV Infections / Q000473:pathology*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D009000:Monocytes / Q000382:microbiology*; D013601:T-Lymphocytes / Q000382:microbiology*; D013997:Time Factors