title: Structural genes, not the LTRs, are the primary determinants of reticuloendotheliosis virus A-induced runting and bursal atrophy.
abstract: Reticuloendotheliosis virus strain A (REV-A) and chicken syncytial virus (CSV), two replication competent avian retroviruses, differ in the extent to which they induce a runting syndrome that includes anemia, lymphoid organ atrophy, and reduced body size. We have isolated an infectious clone of CSV, the less pathogenic of the two viruses, and compared it to REV-A. Partial DNA sequence analysis suggests that it differs from REV-A by no more than 1 to 2% at the nucleotide level. Analysis of viral interference indicates that these two viruses use the same cell receptor for infection of both fibroblasts and hematopoietic cells, DNA sequence of the CSV and REV-A long terminal repeats (LTRs) reveals that these structures differ principally by two small insertions (5 and 19 bp) present in the U3 region of REV-A. The larger of these may encode enhancer sequences that have been reported to influence transcription rates in vitro. Measurement of steady-state levels of viral RNA in infected cells, however, as well as circulating virus in infected chicks indicates that the different pathogenic responses elicited by these two viruses are not due to large differences in viral transcription or replication. Chimeric viruses were constructed in which the LTRs from one virus were used to express the structural genes of the second virus. Infection of 1-day-old chicks by parental virus as well as the reciprocal chimeric constructs demonstrated that the ability to induce both runting and bursal atrophy segregated with the structural genes of REV-A. Infection of birds with additional chimeric viruses in which the env genes of REV-A and CSV were exchanged indicated that the pathogenic response resulting from REV-A infection was due to at least two regions of the viral genome encoding structural genes.
authors.affiliation: Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, California 92037.
authors.forename: E J
authors.initials: EJ
authors.lastname: Filardo
authors.forename: M F
authors.initials: MF
authors.lastname: Lee
authors.forename: E H
authors.initials: EH
authors.lastname: Humphries
mesh_terms: D000740:Anemia / Q000382:microbiology / Q000473:pathology; D000818:Animals; D001284:Atrophy / Q000382:microbiology; D001483:Base Sequence; D002060:Bursa of Fabricius / Q000473:pathology; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D004279:DNA, Viral; D005814:Genes, Viral; D006130:Growth Disorders / Q000382:microbiology; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D017986:Reticuloendotheliosis Viruses, Avian / Q000235:genetics / Q000472:pathogenicity; D001356:Reticuloendotheliosis virus / Q000235:genetics* / Q000472:pathogenicity; D012192:Retroviridae Infections / Q000382:microbiology*; D012689:Sequence Homology, Nucleic Acid; D014412:Tumor Virus Infections / Q000382:microbiology*; D015678:Viral Structural Proteins / Q000235:genetics*
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral; D011991:Receptors, Virus; D015678:Viral Structural Proteins