STRUCTURAL GENES, NOT THE LTRS, ARE THE PRIMARY DETERMINANTS OF RETICULOENDOTHELIOSIS VIRUS A-INDUCED RUNTING AND BURSAL ATROPHY

Reticuloendotheliosis virus strain A (REV-A) and chicken syncytial vir us (CSV), two replication competent avian retroviruses, differ in the extent to which they induce a runting syndrome that includes anemia, l ymphoid organ atrophy, and reduced body size. We have isolated an infe ctious clone of CSV, the less pathogenic of the two viruses, and compa red it to REV-A. Partial DNA sequence analysis suggests that it differ s 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 c ell receptor for infection of both fibroblasts and hematopoietic cells , DNA sequence of the CSV and REV-A long terminal repeats (LTRs) revea ls 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 transc ription rates in vitro. Measurement of steady-state levels of viral RN A 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 transcript ion or replication. Chimeric viruses were constructed in which the LTR s from one virus were used to express the structural genes of the seco nd virus. Infection of 1-day-old chicks by parental virus as well as t he reciprocal chimeric constructs demonstrated that the ability to ind uce both runting and bursal atrophy segregated with the structural gen es of REV-A, Infection of birds with additional chimeric viruses in wh ich the env genes of REV-A and CSV were exchanged indicated that the p athogenic response resulting from REV-A infection was due to at least two regions of the viral genome encoding structural genes. (C) 1994 Ac ademic Press, Inc.