title: Characterization of virulence-associated determinants in the envelope glycoprotein of Pichinde virus.
abstract: We use a small animal model, based on guinea pigs infected with a non-pathogenic Pichinde virus (PICV), to understand the virulence mechanisms of arenavirus infections in the hosts. PICV P2 strain causes a mild febrile reaction in guinea pigs, while P18 causes severe disease with clinical and pathological features reminiscent of Lassa hemorrhagic fever in humans. The envelope glycoproteins (GPC) of P2 and P18 viruses differ at positions 119, 140, and 164, all localized to the receptor-binding G1 subunit. We found that lentiviral pseudotyped virions (VLPs) bearing P18 GPC show more efficient cell entry than those with P2 GPC, and that the E140 residue plays a critical role in this process. Infection of guinea pigs with the recombinant viruses containing the E140K change demonstrated that E140 of GPC is a necessary virulence determinant of P18 infections, possibly by enhancing the ability of virus to enter target cells.
authors.affiliation: Department of Veterinary and Biomedical Sciences, University of Minnesota, Twin Cities, MN 55108, USA.
authors.forename: Naveen
authors.initials: N
authors.lastname: Kumar
authors.forename: Jialong
authors.initials: J
authors.lastname: Wang
authors.forename: Shuiyun
authors.initials: S
authors.lastname: Lan
authors.forename: Shamika
authors.initials: S
authors.lastname: Danzy
authors.forename: Lisa
authors.initials: L
authors.lastname: McLay Schelde
authors.forename: Jill
authors.initials: J
authors.lastname: Seladi-Schulman
authors.forename: Hinh
authors.initials: H
authors.lastname: Ly
authors.forename: Yuying
authors.initials: Y
authors.lastname: Liang
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001117:Arenaviridae Infections / Q000473:pathology / Q000821:virology*; D002460:Cell Line; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006801:Humans; D007835:Lassa Fever / Q000473:pathology / Q000821:virology; D008099:Liver / Q000473:pathology / Q000821:virology*; D009154:Mutation; D018052:Pichinde virus / Q000472:pathogenicity* / Q000502:physiology; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019562:Viral Load; D014774:Virulence; D053586:Virus Internalization
chemical_list: D020033:Protein Isoforms; D021122:Protein Subunits; D014759:Viral Envelope Proteins