Vicenzi E, Panina-Bordignon P, Biswas P, Cota M, Sinigaglla F, Poli G; Conference on Retroviruses and Opportunistic Infections.

Program Abstr 6th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 6th 1999 Chic Ill. 1999 Jan 31-Feb 4; 6th: 165 (abstract no. 520).

San Raffaele Scientific Institute, Milano, Italy.

Macrophage-tropic strains using CCR5 as entry coreceptor predominate during early HIV disease, whereas T-lymphotropic strains utilizing CXCR4 either alone or in combination with CC chemokine receptors, typically emerge later in disease progression. Here we report that R5 HIVs, but not X4 HIVs efficiently replicate in Th1 or Th2 cell lines derived from umbilical human cord blood or in T cell clones obtained from blood of healthy adults. This pattern was neither explained by the absence of functional CXCR4 molecules on the surface of Th1 or Th2 cells, as demonstrated by FACS analysis and chemotactic responses to its ligand SDF-1, nor was it dependent upon expression of endogenous SDF-1. Indeed, X4 HIV entered and reverse transcribed their genomes in Th1 and Th2 cells with efficiency comparable to that of R5 viruses, but substantially failed to spread thereafter unless restimulated by anti-CD3 mAb. HIV-1 env played a major role in determining this restricted pattern of replication in that a chimeric virus in which the X4-dependent gene of LAI was replaced with that of ADA (NL-AD8) efficiently replicated in Th1 and Th2 cells, suggesting that HIV-1 usage of CXCR4 may deliver a negative signal for viral expression. Dualtropic viruses characterized by the simultaneous usage of both chemokine receptors (X4/R5 or X4/R3) selectively replicated in Th2, but not in Th1 cells. These findings suggest that cytokines differentially expressed by either cell type (i.e. IFN-gamma for Th1, IL-4 for Th2, respectively) may play an important role in determining active spreading of these viruses among Th2 lymphocytes, supporting a pathogenic role of this polarized CD4+ T cell subset in HIV disease.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS Vaccines
• Acquired Immunodeficiency Syndrome
• Adult
• Antigens, CD4
• Cell Line
• Chemokine CXCL12
• Chemokines, CC
• Chemokines, CXC
• Disease Progression
• HIV Infections
• HIV Seropositivity
• HIV-1
• Humans
• Interleukin-4
• Receptors, CCR5
• Receptors, CXCR4
• T-Lymphocytes
• Th1 Cells
• Th2 Cells
• immunology

Other ID:

• 20711758

UI: 102195288

From Meeting Abstracts