title: Characterization of a cytolytic strain of equine infectious anemia virus.
abstract: A novel strain of equine infectious anemia virus (EIAV) called vMA-1c that rapidly and specifically killed infected equine fibroblasts (ED cells) but not other infectible cell lines was established. This strain was generated from an avirulent, noncytopathic strain of EIAV, MA-1. Studies with this new cytolytic strain of virus have permitted us to define viral parameters associated with EIAV-induced cell killing and begin to explore the mechanism. vMA-1c infection resulted in induction of rapid cell death, enhanced fusogenic activity, and increased rates of spread in equine fibroblasts compared to other strains of EIAV. The highly cytolytic nature of vMA-1c suggested that this strain might be superinfecting equine fibroblasts. Receptor interference studies demonstrated that prior infection of equine fibroblasts with EIAV did not alter the ability of vMA-1c to infect and kill these cells. In similar studies in a canine fibroblast cell line, receptor interference did occur. vMA-1c infection of equine fibroblasts was also associated with large quantities of unintegrated viral DNA, a well-established hallmark of retroviral superinfection. Cloning of the vMA-1c genome identified nucleotide changes that would result in at least one amino acid change in all viral proteins. A chimeric infectious molecular clone containing the vMA-1c tat, S2, and env open reading frames recapitulated most of the characteristics of vMA-1c, including superinfection, fibroblast killing, and fusogenic activity. In summary, in vitro selection for a strain of EIAV that rapidly killed cells resulted in the generation of a virus that was able to superinfect these cells, presumably by the use of a novel mechanism of cell entry. This phenotype mapped to the 3' half of the genome.
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA. wendy-maury@uiowa.edu
authors.forename: Wendy
authors.initials: W
authors.lastname: Maury
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Wright
authors.forename: Sarahann
authors.initials: S
authors.lastname: Bradley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D004279:DNA, Viral / Q000032:analysis; D005347:Fibroblasts / Q000821:virology*; D006736:Horses; D004860:Infectious Anemia Virus, Equine / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D008969:Molecular Sequence Data; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics; D014774:Virulence
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins