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  • Oral presentation
  • Open Access

Lv4, an activity that restricts nuclear entry of SIVMAC/SIVSM in human blood cells

  • 1, 2,
  • 1,
  • 1,
  • 1,
  • 2,
  • 1,
  • 3 and
  • 1, 4
Retrovirology201310 (Suppl 1) :O28

https://doi.org/10.1186/1742-4690-10-S1-O28

  • Published:

Keywords

  • Peripheral Blood Mononuclear Cell
  • Rhesus Macaque
  • Human Peripheral Blood
  • Leukemia Cell Line
  • Restriction Factor

SIVSM is a lentivirus endemic to the West African sooty mangabey (Cercocebus atys). HIV-2 and SIVMAC are zoonoses that resulted from SIVSM transmission to humans and Asian rhesus macaques (Macaca mulatto), respectively. Human leukemia cell lines, human peripheral blood mononuclear cells and CD4+ T cells, were 4 to 50-fold less permissive for SIVMAC and SIVSM than for HIV-1. In contrast, SIVMAC transduction of human adherent cell lines was equivalent to that of HIV-1. Consistent with adaptation to human cells, HIV-2 was not restricted as potently as was SIVMAC. SIVMAC transduction of human blood cells was rescued up to the level of HIV-1 by As2O3, a compound that increases the infectivity of viruses in the context of TRIM5-mediated restriction. Nonetheless, efficient knockdown of TRIM5 or cyclophilin A, a cytoplasmic factor that sometimes regulates TRIM5 restriction activity, did not rescue SIVMAC tranduction of these cells. Substitution of HIV-1 CA with the CA from SIVMAC rendered HIV-1 poorly infectious for Jurkat T cells. The block occurred after completion of reverse transcription and the formation of 2-LTR circles, but before establishment of the provirus. Heterokaryons resulting from fusion of permissive with restrictive cells exhibited the restrictive phenotype, indicating that SIV transduction of human blood cells is inefficient due to a dominant-acting restriction factor. These results demonstrate that the nucleus of human blood cells possesses a TRIM5-like restriction factor specific for the SIVMAC/SIVSM capsid and that, by extension, cross-species transmission of SIV SM to human cells necessitated adaptation of HIV-2 to this restriction factor.

Authors’ Affiliations

(1)
Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland
(2)
Center for Integrative Biology, University of Trento, Trento, Italy
(3)
Laboratory of Retrovirology, University of Quebec, Trois-Rivières, Canada
(4)
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, USA

Copyright

© Pizzato et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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