Baumann J, Ahn G, Unutmaz D, KewalRamani V; Conference on Retroviruses and Opportunistic Infections.

Abstr 10th Conf Retrovir Oppor Infect Feb 10 14 2003 Hynes Conv Cent Boston Mass USA Conf Retrovir Oppor Infect 10th 2003 Boston Mass. 2003 Feb 10-14; 10: abstract no. 277.

Natl Cancer Inst at Frederick, MD

BACKGROUND: Expression of murine or human CXCR4 with human CD4 renders mouse fibroblasts susceptible to transduction by X4-tropic HIV-1. In contrast, murine T-cells expressing the same factors are refractory to infection by X4-tropic HIV-1. No such infection block is observed for R5-tropic HIV-1 isolates in murine T-cells expressing human CD4 and CCR5. Surprisingly, MLV pseudotyped with X4-tropic HIV-1 Env has been reported to efficiently transduce murine T-cells expressing HIV-1 receptor molecules. Based on this observation, we investigated what unique properties of X4-tropic MLV versus X4-tropic HIV-1 permitted infection. We also further investigated the nature of the X4-tropic HIV-1 infection block.METHODS: Single-round infection assays were performed using retroviral vectors carrying reporter genes to monitor successful infection events. Viral entry in different targe T-cells was also examined via real-time PCR for early stage reverse transcriptase products. Cell-cell fusions were observed via light microscopy, FACS analysis, and enzyme diffusion assays.RESULTS: MLV-pseudotypes with cytoplasmic truncations of X4-tropic HIV-1 Env were able to transduce human CD4/CXCR4 expressing murine T-cells. In order to determine if relief of the infection block was due to 1) truncations in HIV-1 Env or 2) MLV core elements, we first tested HIV-1 vectors pseudotyped with truncated HIV envelope variants in challenges of murine T-cells. HIV vectors bearing wild-type or truncated Env were inefficient in transduction. However, MLV vectors, particularly those displaying truncated HIV-1 Env, efficiently transduced the T-cells. Co-culture assays using human cells expressing wild-type and truncated X4-tropic HIV-1 Env were competent to fuse with the murine T-cells.CONCLUSIONS: In contrast to CCR5, CXCR4 function as an HIV-1 co-receptor appears to be cell-type dependent. MLV vectors do not manifest the same restrictions for reasons which are unclear. Blocks in HIV-1 infection in murine T-cells with X4-tropic HIV-1 may be at a post-entry step, although no such block is observed with R5-tropic HIV-1. This would suggest a role for CXCR4 in the post-fusion trafficking of HIV-1 in targe T-cells as well as differences of these routes in CXCR4 and CCR5 mediated infections.

Publication Types:

• Meeting Abstracts

Keywords:

• Acquired Immunodeficiency Syndrome
• Animals
• Anti-HIV Agents
• Antigens, CD4
• Genes, env
• Genetic Vectors
• HIV
• HIV Core Protein p24
• HIV Envelope Protein gp120
• HIV Envelope Protein gp41
• HIV Infections
• HIV-1
• Humans
• Leukemia Virus, Murine
• Membrane Fusion
• Mice
• Moloney murine leukemia virus
• Muridae
• Receptors, CCR5
• Receptors, CXCR4
• Receptors, HIV
• T-Lymphocytes
• genetics
• immunology

Other ID:

• GWAIDS0021235

UI: 102260859

From Meeting Abstracts