title: Unique spectrum of activity of prosimian TRIM5alpha against exogenous and endogenous retroviruses.
abstract: Lentiviruses, the genus of retrovirus that includes HIV-1, rarely endogenize. Some lemurs uniquely possess an endogenous lentivirus called PSIV ("prosimian immunodeficiency virus"). Thus, lemurs provide the opportunity to study the activity of host defense factors, such as TRIM5α, in the setting of germ line invasion. We characterized the activities of TRIM5α proteins from two distant lemurs against exogenous retroviruses and a chimeric PSIV. TRIM5α from gray mouse lemur, which carries PSIV in its genome, exhibited the narrowest restriction activity. One allelic variant of gray mouse lemur TRIM5α restricted only N-tropic murine leukemia virus (N-MLV), while a second variant restricted N-MLV and, uniquely, B-tropic MLV (B-MLV); both variants poorly blocked PSIV. In contrast, TRIM5α from ring-tailed lemur, which does not contain PSIV in its genome, revealed one of the broadest antiviral activities reported to date against lentiviruses, including PSIV. Investigation into the antiviral specificity of ring-tailed lemur TRIM5α demonstrated a major contribution of a 32-amino-acid expansion in variable region 2 (v2) of the B30.2/SPRY domain to the breadth of restriction. Data on lemur TRIM5α and the prediction of ancestral simian sequences hint at an evolutionary scenario where antiretroviral specificity is prominently defined by the lineage-specific expansion of the variable loops of B30.2/SPRY.
authors.affiliation: Institute of Microbiology, University Hospital Center and University of Lausanne, CHUV 1011 Lausanne, Switzerland.
authors.forename: Nadia
authors.initials: N
authors.lastname: Rahm
authors.forename: Melvyn
authors.initials: M
authors.lastname: Yap
authors.forename: Joke
authors.initials: J
authors.lastname: Snoeck
authors.forename: Vincent
authors.initials: V
authors.lastname: Zoete
authors.forename: Miguel
authors.initials: M
authors.lastname: Muñoz
authors.forename: Ute
authors.initials: U
authors.lastname: Radespiel
authors.forename: Elke
authors.initials: E
authors.lastname: Zimmermann
authors.forename: Olivier
authors.initials: O
authors.lastname: Michielin
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Stoye
authors.forename: Angela
authors.initials: A
authors.lastname: Ciuffi
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016000:Cluster Analysis; D019143:Evolution, Molecular; D007900:Lemur / Q000276:immunology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012190:Retroviridae / Q000276:immunology*; D017386:Sequence Homology, Amino Acid
chemical_list: D002352:Carrier Proteins