Structural, biochemical, and in vivo characterization of the first virally encoded cyclophilin from the Mimivirus.
Although multiple viruses utilize host cell cyclophilins, including severe acute respiratory syndrome (SARS) and human immunodeficiency virus type-1(HIV-1), their role in infection is poorly understood. To help elucidate these roles, we have characterized the first virally encoded cyclophilin (mimicyp) derived from the largest virus discovered to date (the Mimivirus) that is also a causative agent of pneumonia in humans. Mimicyp adopts a typical cyclophilin-fold, yet it also forms trimers unlike any previously characterized homologue. Strikingly, immunofluorescence assays reveal that mimicyp localizes to the surface of the mature virion, as recently proposed for several viruses that recruit host cell cyclophilins such as SARS and HIV-1. Additionally mimicyp lacks peptidyl-prolyl isomerase activity in contrast to human cyclophilins. Thus, this study suggests that cyclophilins, whether recruited from host cells (i.e. HIV-1 and SARS) or virally encoded (i.e. Mimivirus), are localized on viral surfaces for at least a subset of viruses.
Thai
Vu
V
Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02454, USA.
Renesto
Patricia
P
Fowler
C Andrew
CA
Brown
Darin J
DJ
Davis
Tara
T
Gu
Wanjun
W
Pollock
David D
DD
Kern
Dorothee
D
Raoult
Didier
D
Eisenmesser
Elan Z
EZ
D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D021984:Cyclophilin A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021983:Cyclophilins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004267:DNA Viruses / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011487:Protein Conformation; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000737:chemistry / Q000378:metabolism
D008024:Ligands; D014764:Viral Proteins; C089504:polyphosphoinositide phosphatase; D010744:Phosphoric Monoester Hydrolases; D021984:Cyclophilin A; D021983:Cyclophilins