The LEM domain proteins emerin and LAP2alpha are dispensable for human immunodeficiency virus type 1 and murine leukemia virus infections.

Abstract

The human nuclear envelope proteins emerin and lamina-associated polypeptide 2alpha (LAP2alpha) have been proposed to aid in the early replication steps of human immunodeficiency virus type 1 (HIV-1) and murine leukemia virus (MLV). However, whether these factors are essential for HIV-1 or MLV infection has been questioned. Prior studies in which conflicting results were obtained were highly dependent on RNA interference-mediated gene silencing. To shed light on these contradictory results, we examined whether HIV-1 or MLV could infect primary cells from mice deficient for emerin, LAP2alpha, or both emerin and LAP2alpha. We observed HIV-1 and MLV infectivity in mouse embryonic fibroblasts (MEFs) from emerin knockout, LAP2alpha knockout, or emerin and LAP2alpha double knockout mice to be comparable in infectivity to wild-type littermate-derived MEFs, indicating that both emerin and LAP2alpha were dispensable for HIV-1 and MLV infection of dividing, primary mouse cells. Because emerin has been suggested to be important for infection of human macrophages by HIV-1, we also examined HIV-1 transduction of macrophages from wild-type mice or knockout mice, but again we did not observe a difference in susceptibility. These findings prompted us to reexamine the role of human emerin in supporting HIV-1 and MLV infection. Notably, both viruses efficiently infected human cells expressing high levels of dominant-negative emerin. We thus conclude that emerin and LAP2alpha are not required for the early replication of HIV-1 and MLV in mouse or human cells.

• Authors: Alok Mulky, Tatiana V Cohen, Serguei V Kozlov, Barbara Korbei, Roland Foisner, Colin L Stewart, Vineet N KewalRamani
• Journal: Journal of virology (J Virol) Vol. 82 Issue 12 Pg. 5860-8 (Jun 2008) ISSN: 1098-5514 [Electronic] United States
• PMID: 18400857 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• DNA-Binding Proteins
• Membrane Proteins
• Nuclear Proteins
• emerin
• lamina-associated polypeptide 2

Topics

• Animals
• Cell Line
• Cells, Cultured
• DNA-Binding Proteins (genetics, metabolism)
• Embryo, Mammalian (cytology)
• Fibroblasts (metabolism)
• HIV-1 (physiology)
• Humans
• Kidney (cytology)
• Leukemia Virus, Murine (pathogenicity)
• Membrane Proteins (genetics, metabolism)
• Mice
• Mice, Knockout
• NIH 3T3 Cells
• Nuclear Proteins (genetics, metabolism)
• Protein Structure, Tertiary
• Retroviridae Infections (metabolism)