Moir S, Malaspina A, Lapointe R, Ostrowski M, Justement S, Mizell S, Hwu P, Fauci AS; 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. 519).
National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
HIV-1 replicates primarily in lymphoid tissues where virus has ready access to activated immune cells. Interactions between antigen presenting cells and T cells involving CD40 and CD40L respectively contribute to this hyperactivity. We studied soluble CD40L/IL-4-mediated proliferation of PBMC-derived B cells in vitro. Pure B cell cultures expressing high levels of costimulatory/activation markers were generated with parallel upregulation of HIV-1 receptors CD4 and X4, but not CCR5. Infection with single-round competent luciferase viruses complemented with either ampho- or HIV-derived envelopes showed that the temporal modulation of HIV-1 receptors correlated with susceptibility of the B cells to dual-tropic and T-tropic strains of HIV-1 and resistance to M-tropic strains. HIV-mediated activity was abolished with an anti-CD4 MAb or an X4-blocking peptide, both of which had no effect on entry of virus pseudotyped with amphotropic envelope. Full virus replication kinetics confirmed that infection is restricted to X4-using viruses and revealed that productive replication occurred rapidly, in the absence of cytopathicity, although the infected cells readily formed syncytia with cocultured T cells. These findings demonstrate the potential for a highly activated immunological environment to induce the expression of HIV-1 receptors on B cells that primes them for infection with selective strains of HIV-1. We are currently investigating the relevance of these observations in vivo.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Anti-HIV Agents
- Antigens, CD4
- Antigens, CD40
- B-Lymphocytes
- CD40 Ligand
- Disease Susceptibility
- Gene Expression
- HIV
- HIV Infections
- HIV-1
- In Vitro
- Lymphoid Tissue
- Receptors, CCR5
- Receptors, CXCR4
- T-Lymphocytes
- Up-Regulation
- Virus Replication
- genetics
- immunology
- virology
Other ID:
UI: 102195287
From Meeting Abstracts