title: 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.
abstract: 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.
authors.affiliation: Central Laboratory, Netherlands Red Cross Blood Transfusion Service, Amsterdam.
authors.forename: H
authors.initials: H
authors.lastname: Schuitemaker
authors.forename: M
authors.initials: M
authors.lastname: Koot
authors.forename: N A
authors.initials: NA
authors.lastname: Kootstra
authors.forename: M W
authors.initials: MW
authors.lastname: Dercksen
authors.forename: R E
authors.initials: RE
authors.lastname: de Goede
authors.forename: R P
authors.initials: RP
authors.lastname: van Steenwijk
authors.forename: J M
authors.initials: JM
authors.lastname: Lange
authors.forename: J K
authors.initials: JK
authors.lastname: Schattenkerk
authors.forename: F
authors.initials: F
authors.lastname: Miedema
authors.forename: M
authors.initials: M
authors.lastname: Tersmette
mesh_terms: 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