Comparison of the convergent receptor utilization of a retargeted feline leukemia virus envelope with a naturally-occurring porcine endogenous retrovirus A

• Published in: Virology (New York, N.Y.) Vol. 427; no. 2; pp. 118 - 126
• Main Authors: Mazari, Peter M, Argaw, Takele, Valdivieso, Leonardo, Zhang, Xia, Marcucci, Katherine T, Salomon, Daniel R, Wilson, Carolyn A, Roth, Monica J
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.06.2012
• Subjects: Amino Acid Sequence; Amino acids; Animals; Cats; Cell Line; Chimeras; Endogenous Retroviruses - metabolism; Envelopes; Feline leukemia; Feline leukemia virus; FeLV CP Env isolate; Gene Expression Regulation, Viral; Homology; Human PAR-1 receptor; Human PAR-2 receptor; Humans; Infectious Disease; Leukemia Virus, Feline - physiology; Mutation; Point mutation; Porcine endogenous retrovirus; Porcine endogenous retrovirus A (PERV A); Protein Binding; Proteinase-activated receptor 1; Receptors, Cell Surface - physiology; Recombinant Proteins; Retroviral receptors; Retrovirus; Swine; Viral entry; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - genetics; Viral Envelope Proteins - metabolism; Viral Tropism; Virus Internalization; Viral entry; Human PAR-2 receptor; Human PAR-1 receptor; Feline leukemia virus; FeLV CP Env isolate; Retroviral receptors; Porcine endogenous retrovirus A (PERV A)
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2012.02.012

Abstract In vitro screening of randomized FeLV Envelope libraries identified the CP isolate, which enters cells through HuPAR-1, one of two human receptors utilized by porcine endogenous retrovirus-A (PERV-A), a distantly related gammaretrovirus. The CP and PERV-A Envs however, share little amino acid homology. Their receptor utilization was examined to define the common receptor usage of these disparate viral Envs. We demonstrate that the receptor usage of CP extends to HuPAR-2 but not to the porcine receptor PoPAR, the cognate receptor for PERV-A. Reciprocal interference between virus expressing CP and PERV-A Envs was observed on human cells. Amino acid residues localized to within the putative second extracellular loop (ECL-2) of PAR-1 and PAR-2 are found to be critical for CP envelope function. Through a panel of receptor chimeras and point mutations, this area was also found to be responsible for the differential usage of the PoPAR receptor between CP and PERV-A.