Requirement for the second coding exon of Tat in the optimal replication of macrophage-tropic HIV-1

J Biomed Sci. 2003;10(6 Pt 1):651-60. doi: 10.1159/000073531.

Abstract

HIV-1 Tat is essential for virus replication and is a potent transactivator of viral gene expression. Evidence suggests that Tat also influences virus infectivity and cytopathicity. Here, we find that the second coding exon of Tat contributes a novel function for the replication/infectivity of macrophage-tropic HIV-1. We show that macrophage-tropic HIV-1 which expresses the full-length two-exon form of Tat replicates better in monocyte-derived macrophages (MDM) than an otherwise isogenic virus which expresses only the one-exon form of Tat. Similarly, two-exon Tat expressing HIV-1 also replicates better than one-exon Tat expressing HIV-1 in two different models of human cells/tissue reconstituted SCID mice.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Exons*
  • Gene Expression Regulation, Viral*
  • Gene Products, tat / genetics*
  • Gene Products, tat / metabolism
  • HIV-1* / genetics
  • HIV-1* / physiology
  • Humans
  • Liver / metabolism
  • Liver / virology
  • Macrophages / immunology
  • Macrophages / virology*
  • Mice
  • Mice, SCID
  • Open Reading Frames
  • Proviruses / genetics
  • Proviruses / metabolism
  • Thymus Gland / metabolism
  • Thymus Gland / virology
  • Transcription, Genetic
  • Virus Replication / genetics*
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • Gene Products, tat
  • tat Gene Products, Human Immunodeficiency Virus