Fragile X mental retardation protein restricts replication of human immunodeficiency virus type 1.
Gag protein is the major structural component of human immunodeficiency virus type 1 (HIV-1) particles and drives virus assembly on cellular membranes. This function of Gag is attributed to its intrinsic self-multimerization ability as well as its interaction with cellular factors such as TSG101 that binds to the PTAP sequence in the p6 region of Gag and promotes HIV-1 budding through recruiting the ESCRT (endosomal sorting complex required for transport). As a result of its essential role in virus assembly, Gag also becomes the target of cellular restriction factors such as APOBEC3G and Trim5alpha. In this study, we report that the fragile X mental retardation protein (FMRP) interacts with HIV-1 Gag and is packaged into virus particles. Although knockdown of FMRP does not markedly affect production of virus particles, infectivity of HIV-1 virions was significantly decreased. Consistent with this observation, overexpression of the wild type FMRP, but not the FMRP mutants that lack the KH1 or the KH2 domains, led to 2- to 3-fold reduction of virus infectivity. Together, these results suggest that FMRP diminishes HIV-1 infectivity through association with viral Gag protein and virus particles.
Pan
Qinghua
Q
McGill AIDS Centre, Lady Davis Institute-Jewish General Hospital, 3755 Cote Ste-Catherine Road, Montreal, Quebec, Canada H3T 1E2.
Rong
Liwei
L
Zhao
Xiaoyan
X
Liang
Chen
C
D018929:Cell Culture Techniques; D015536:Down-Regulation; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D015683:Gene Products, gag / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D019169:Jurkat Cells; D011485:Protein Binding; D012367:RNA, Viral / Q000032:analysis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014771:Virion / Q000378:metabolism / Q000472:pathogenicity; D019065:Virus Assembly; D014779:Virus Replication
D051860:Fragile X Messenger Ribonucleoprotein 1; D015683:Gene Products, gag; D012367:RNA, Viral; D016601:RNA-Binding Proteins