Racz, P.

Broadening of coreceptor usage by human immunodeficiency virus type 2 does not correlate with increased pathogenicity in an in vivo model. (Article)

2000-01-01T00:00:00Z

The pathogenic properties of four primary human immunodeficiency virus type 2 (HIV-2) isolates and two primary HIV-2 biological clones were studied in an in vivo human-to-mouse chimeric model. The cell-associated viral load and the ability to reduce the severity of the induced graft-versus-host disease symptoms, the CD4/CD8 ratio and the level of repopulation of the mouse tissues by the graft, were determined. All HIV-2 strains, irrespective of their in vitro biological phenotype, replicated to high titres and significantly reduced graft-versus-host disease symptoms as well as the CD4/CD8 ratios. Reduction of graft repopulation caused by infection with the respective HIV-2 strains showed that the in vitro replication rate, syncytium-inducing capacity and ability to infect human macrophages did influence the in vivo pathogenic potential whereas broadening of coreceptor usage did not.

CD4 T cells remain the major source of HIV-1 during end stage disease. (Article)

1999-01-01T00:00:00Z

OBJECTIVE: To assess the source of HIV-1 production in lymphoid tissue biopsies from HIV-infected patients, with no prior anti-retroviral protease inhibitor treatment, with a CD4 cell count > 150 x 10(6)/l (group I) or < 50 x 10(6)/l (group II), co-infected with Mycobacterium tuberculosis or Mycobacterium avium complex. DESIGN AND METHODS: Lymphoid tissue biopsies from 11 HIV-1-infected patients, taken for diagnostic purposes, were studied by HIV-1 RNA in situ hybridization and immunohistochemistry. RESULTS: Patients of group I showed well organized granulomas, in contrast with patients of group II, in which granuloma formation was absent. HIV-1 RNA-positive cells in group I patients were found mainly around the granulomas, whereas in group II HIV-1-producing cells were confined to areas with remaining intact lymphoid tissue. Despite the abundant presence of macrophages, the productively infected HIV-1-positive cells in both groups were almost exclusively CD4 T cells. CONCLUSION: In contrast with previously published data, CD4 T cells appear to remain the major source of HIV-1 production in end-stage disease.

Human antibodies that neutralize primary human immunodeficiency virus type 1 in vitro do not provide protection in an in vivo model. (Article)

1996-01-01T00:00:00Z

Recently, conflicting data have been published about the ability of antibodies which efficiently neutralize T cell-adapted human immunodeficiency virus type 1 (HIV-1) strains to neutralize primary HIV-1 strains in vitro and in vivo. Here we present data indicating that such antibodies fail to neutralize primary HIV-1 strains in vivo. To this end, a newly developed chimeric human-to-mouse model was used, in which several aspects of primary HIV-1 infection are mimicked. Poly- and monoclonal antibodies protected the grafted human cells, in a dose-dependent way, from infection with T cell-adapted HIV-1 in this system. A human monoclonal antibody specific for the CD4 binding domain that efficiently neutralizes HIV-1 IIIB in vitro did not protect the human graft from HIV-1 IIIB infection. None of the antibodies provided protection in the in vivo model against infection with primary HIV-1 strains, although they were able to neutralize these same strains in vitro.