Cyclosporine increases human immunodeficiency virus type 1 vector transduction of primary mouse cells.
Murine primary cells are poorly permissive to human immunodeficiency virus type 1 (HIV-1) vector infection. Retroviral infectivity is influenced by dominant inhibitors such as TRIM5alpha. Sensitivity to TRIM5alpha is altered by interactions between cyclophilin A and the HIV-1 capsid. Here we demonstrate that competitive inhibitors of cyclophilins, cyclosporine or the related Debio-025, stimulate HIV-1 vector transduction of primary murine cells, including bone marrow and macrophages, up to 20-fold. Unexpectedly, the infectivity of an HIV-1 mutant or a simian lentivirus that does not recruit cyclophilin A is also stimulated by these drugs. We propose that cyclosporine and related compounds will be useful tools for experimental infection of murine primary cells. It is possible that HIV-1 infection of murine cells is inhibited by dominant factors related to immunophilins.
Noser
Josh A
JA
Molecular Medicine Program, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Towers
Greg J
GJ
Sakuma
Ryuta
R
Dumont
Jean-Maurice
JM
Collins
Mary K L
MK
Ikeda
Yasuhiro
Y
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000821:virology; D021984:Cyclophilin A / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000187:drug effects; D005260:Female; D005822:Genetic Vectors; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016086:Lentivirus / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D021984:Cyclophilin A