The LEM domain proteins emerin and LAP2alpha are dispensable for human immunodeficiency virus type 1 and murine leukemia virus infections.
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.
Mulky
Alok
A
HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA.
Cohen
Tatiana V
TV
Kozlov
Serguei V
SV
Korbei
Barbara
B
Foisner
Roland
R
Stewart
Colin L
CL
KewalRamani
Vineet N
VN
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000166:cytology; D009052:Leukemia Virus, Murine / Q000472:pathogenicity; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012192:Retroviridae Infections / Q000378:metabolism*
D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; C092710:emerin; C093413:lamina-associated polypeptide 2