HIV-1 capsid-targeting domain of cleavage and polyadenylation specificity factor 6.
The antiviral factor CPSF6-358 restricts human immunodeficiency virus type 1 (HIV-1) infection through an interaction with capsid (CA), preventing virus nuclear entry and integration. HIV-1 acquires resistance to CPSF6-358 through an N74D mutation of CA that impairs binding of the antiviral factor. Here we examined the determinants within CPSF6-358 that are necessary for CA-specific interaction. Residues 314 to 322 include amino acids that are essential for CPSF6-358 restriction of HIV-1. Fusion of CPSF6 residues 301 to 358 to rhesus TRIM5α is also sufficient to restrict wild-type but not N74D HIV-1. Restriction is lost if CPSF6 residues in the amino acid 314 to 322 interaction motif are mutated. Examination of the CA targeting motif in CPSF6-358 did not reveal evidence of positive selection. Given the sensitivity of different primate lentiviruses to CPSF6-358 and apparent conservation of this interaction, our data suggest that CPSF6-358-mediated targeting of HIV-1 could provide a broadly effective antiviral strategy.
HIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland, USA.
Kyeongeun
K
Lee
Alok
A
Mulky
Wendy
W
Yuen
Thomas D
TD
Martin
Nicholas R
NR
Meyerson
Laura
L
Choi
Hyun
H
Yu
Sara L
SL
Sawyer
Vineet N
VN
Kewalramani
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002213:Capsid / Q000378:metabolism*; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011323:Primates; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics* / Q000378:metabolism*
C450562:cleavage factor Im, human; D039221:mRNA Cleavage and Polyadenylation Factors