title: Arterivirus minor envelope proteins are a major determinant of viral tropism in cell culture.
abstract: Arteriviruses are enveloped positive-strand RNA viruses for which the attachment proteins and cellular receptors have remained largely controversial. Arterivirus particles contain at least eight envelope proteins, an unusually large number among RNA viruses. These appear to segregate into three groups: major structural components (major glycoprotein GP5 and membrane protein [M]), minor glycoproteins (GP2a, GP3, and GP4), and small hydrophobic proteins (E and the recently discovered ORF5a protein). Biochemical studies previously suggested that the GP5-M heterodimer of porcine reproductive and respiratory syndrome virus (PRRSV) interacts with porcine sialoadhesin (pSn) in porcine alveolar macrophages (PAM). However, another study proposed that minor protein GP4, along with GP2a, interacts with CD163, another reported cellular receptor for PRRSV. In this study, we provide genetic evidence that the minor envelope proteins are the major determinant of arterivirus entry into cultured cells. A PRRSV infectious cDNA clone was equipped with open reading frames (ORFs) encoding minor envelope and E proteins of equine arteritis virus (EAV), the only known arterivirus displaying a broad tropism in cultured cells. Although PRRSV and EAV are only distantly related and utilize diversified transcription-regulating sequences (TRSs), a viable chimeric progeny virus was rescued. Strikingly, this chimeric virus (vAPRRS-EAV2ab34) acquired the broad in vitro cell tropism of EAV, demonstrating that the minor envelope proteins play a critical role as viral attachment proteins. We believe that chimeric arteriviruses of this kind will be a powerful tool for further dissection of the arterivirus replicative cycle, including virus entry, subgenomic RNA synthesis, and virion assembly.
authors.affiliation: Department of Swine Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
authors.forename: Debin
authors.initials: D
authors.lastname: Tian
authors.forename: Zuzhang
authors.initials: Z
authors.lastname: Wei
authors.forename: Jessika C
authors.initials: JC
authors.lastname: Zevenhoven-Dobbe
authors.forename: Runxia
authors.initials: R
authors.lastname: Liu
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Tong
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Snijder
authors.forename: Shishan
authors.initials: S
authors.lastname: Yuan
mesh_terms: D000818:Animals; D018174:Arterivirus Infections / Q000662:veterinary* / Q000821:virology; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D007240:Equartevirus / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D019318:Porcine Reproductive and Respiratory Syndrome / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000235:genetics / Q000502:physiology*; D013552:Swine; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D056189:Viral Tropism
chemical_list: D014759:Viral Envelope Proteins