Influence of env and long terminal repeat sequences on the tissue tropism of avian leukosis viruses

Abstract

Adsorption and penetration of retroviruses into eucaryotic cells is mediated by retroviral envelope glycoproteins interacting with host receptors. Recombinant avian leukosis viruses (ALVs) differing only in envelope determinants that interact with host receptors for subgroup A or E ALVs have been found to have unexpectedly distinctive patterns of tissue-specific replication. Recombinants of both subgroups were highly expressed in bursal lymphocytes as well as in cultured chicken embryo fibroblasts. In contrast, the subgroup A but not subgroup E host range allowed high levels of expression in skeletal muscle, while subgroup E but not subgroup A envelope glycoproteins permitted efficient replication in the thymus. A subgroup B virus (RAV-2), like the subgroup E viruses, demonstrated a distinct bursal and thymic tropism, further supporting the theory that genes encoding receptors for subgroup B and E viruses are allelic. The source of long terminal repeats (LTRs) or adjacent sequences also influenced tissue-specific replication, with the LTRs from endogenous virus RAV-O supporting efficient replication in the bursa and thymus but not in skeletal muscle. These results indicate that ALV env and LTR regions are responsible for unexpectedly distinctive tissue tropisms.

Viral determinants of simian immunodeficiency virus (SIV) virulence in rhesus macaques assessed by using attenuated and pathogenic molecular clones of SIVmac

“…In addition, analysis of the pair of recombinant viruses, in which only the external domain of env was exchanged, demonstrated that this portion of the viral genome is not the sole determinant of levels of virus load, titers of antiviral immune responses, or pathogenic potential. These results are consistent with those from studies on other retroviruses in which virulence was also found to be influenced by multiple, separate regions of the viral genome (4,48).…”

Transformation of chicken myelomonocytic cells by a retrovirus expressing the v-myb oncogene from the long terminal repeats of avian myeloblastosis virus but not Rous sarcoma virus

“…Our in vitro transformation results have shown that infection of avian myelomonocytic cells with a virus expressing the v-myb oncogene from AMV LTRs leads to phenotypic transformation, while infection with a similar v-myb-expressing virus carrying RSV LTRs fails to transform the same cells. The expression and pathogenicity of avian retroviruses is usually determined by both the strength of the LTR enhancer (6,10,36) and the interaction of the envelope protein with its target cell receptor (7). gag and pol sequences can, however, also determine viral pathogenicity by a specific LTR in some avian retroviruses without oncogenes (6).…”

“…In contrast, the LTRs of these two viruses share nearly identical sequences in the R and U5 regions but have extensive sequence divergence in the U3 region (31). The U3 region of avian retroviral LTRs contains the enhancer sequences that bind cell type-specific transcription factors and determine both the pathogenicity of oncogene-containing viruses (6, 36) and their tissue tropism (7). Our results show that infection of chicken embryo spleen cell cultures with either wild-type AMV or the replicationcompetent virus expressing v-myb from AMV LTRs (RCAMV-v-myb) results in phenotypic myelomonocytic cell transformation.…”

A new avian leukosis virus-based packaging cell line that uses two separate transcomplementing helper genomes

“…Such a defective packaging cell line would be an intermediate to generate genuine helper cell lines expressing the env genes of different subgroup specificities. Such a system would allow production of different pseudotypes of the same retroviral vector to transfer exogenous genes into various tissues expressing different retrovirus receptors (5,6). On the other hand, coculture of packaging cell lines expressing different host range envelopes could be used to amplify a retroviral vector stock throught multiple rounds of infection by avoiding the barrier of interference (2).…”