UMMS Affiliation

Program in Molecular Medicine

Date

4-29-2004

Document Type

Article

Subjects

Cell Differentiation; Cells, Cultured; DNA-Binding Proteins; HIV-1; Humans; Macrophages; Monocytes; NFATC Transcription Factors; *Nuclear Proteins; Thymine Nucleotides; Transcription Factors; Transcription, Genetic; Virus Replication

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Tissue macrophages are an important cellular reservoir for replication of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus. In vitro, the ability of macrophages to support viral replication is differentiation dependent in that precursor monocytes are refractory to infection. There is, however, no consensus as to the exact point at which infection is restricted in monocytes. We have revisited this issue and have compared the efficiencies of early HIV-1 replication events in monocytes and in differentiated macrophages. Although virus entry in monocytes was comparable to that in differentiated macrophages, synthesis of full-length viral cDNAs was very inefficient. Relative to differentiated macrophages, monocytes contained low levels of dTTP due to low thymidine phosphorylase activity. Exogenous addition of D-thymidine increased dTTP levels to that in differentiated macrophages but did not correct the reverse transcription defect. These results point to a restriction in monocytes that is independent of reverse transcription precursors and suggest that differentiation-dependent cellular cofactors of reverse transcription are rate limiting in monocytes.

Rights and Permissions

Citation: J Virol. 2004 May;78(10):5523-7.

Related Resources

Link to Article in PubMed

Journal Title

Journal of virology

PubMed ID

15113933

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