L. N. Payne

Host range of Rous sarcoma virus pseudotype RSV(HPRS-103) in 12 avian species: support for a new avian retrovirus envelope subgroup, designated J

The host ranges of the Rous sarcoma virus (RSV) pseudotype RSV(HPRS-103) of a novel avian leukosis virus (ALV), strain HPRS-103, and representative RSV pseudotypes of subgroups A to F, have been determined in embryo fibroblasts from 12 avian species. Domestic fowl, red jungle fowl, Sonnerats jungle fowl and turkey were susceptible to infection by RSV(HPRS-103); ring-necked pheasant, Japanese green pheasant, golden pheasant, Japanese quail, guinea-fowl, Peking duck, Muscovy duck and goose were resistant. The host range pattern of RSV(HPRS-103) differs from those of viruses of subgroups A to G and I, and provides support for placing the HPRS-103 strain of ALV in a new envelope subgroup, designated J.

The long view: 40 years of avian leukosis research

The present review is aimed at the non-specialist reader and is one of a number being written on important diseases of poultry to celebrate the 40th anniversary of the birth of Avian Pathology, the journal of the World Veterinary Poultry Association. The diseases of the avian leukosis complex have a number of features of distinction. They were the first neoplastic diseases in any species to be shown, 100 years ago, to be transmissible and caused by viruses, and have consequently been studied extensively by biomedical scientists as models for the role of viruses in cancer. They also became, from around the 1920s, the major cause of mortality and economic loss to the developed poultry industry, and were studied by agricultural scientists searching to understand and control them. The remit of the review is to cover research carried out over the 40 years since 1971, when the journal was founded. In this review on avian leukosis, an introductory summary is given of knowledge acquired over the preceding 60 years. Subsequently a selection is provided of discoveries, both fundamental and more applied, that seem to us to be of particular importance and interest. Much of the work was carried out by biomedical scientists interested in cancer. Probably the most significant was the discovery in the avian retroviruses of oncogenes that cause leukosis and other tumours and of their origin from proto-oncogenes in normal cells. These oncogenes are involved in cancer in many species, including chickens and humans. Other work was performed by agricultural scientists interested in poultry disease. Interests of the two groups have overlapped, particularly as a result of a shift of emphasis to molecular biology research.

Antigenic variants of J subgroup avian leukosis virus: sequence analysis reveals multiple changes in the env gene.

HPRS-103, the prototype of avian leukosis virus (ALV) subgroup J, was isolated in 1989 from meat-type chickens from commercial flocks where it induces myelocytic myeloid leukosis (ML). The HPRS-103 env gene differs considerably from other ALV subgroups but shows high identity (75-97%) to env-like sequences of the different members of the EAV family of endogenous avian retroviruses. Recently, we have isolated several viruses related to HPRS-103 from cases of ML. Although these isolates showed properties of ALV subgroup J, the majority of them resisted neutralization by HPRS-103-specific serum, suggesting antigenic variation. The nucleotide sequence of the env gene of the variant viruses showed several substitutions resulting in amino acid changes especially clustered in the variable regions hr1, hr2 and vr3. Analysis of the data suggests that selection pressure, probably from the immune response, is driving the antigenic variation among the isolates. Phylogenetic analysis of the sequences showed the evolutionary relationships of the isolates with HPRS-103 and the EAV family of endogenous avian retroviruses. The epidemiological significance of the antigenic variation and the emergence of variant viruses are discussed.

HPRS‐103: A retro virus strikes back. The emergence of subgroup J avian leukosis virus

In 1988, a new strain of avian leukosis virus (ALV) was isolated from meat‐type chickens in the UK. Studies on the prototype virus strain, HPRS‐103, placed it in a new envelope subgroup, designated J. The envelope gene of subgroup J ALV (ALV‐J) is closely related to endogenous retroviral sequences of the EAV family present in the normal chicken genome, suggesting that ALV‐J is a genetic recombinant. Sequence studies on the envelope gene of various field isolates of ALV‐J indicate the occurrence of frequent mutations leading to antigenic variation. Experimentally and in the field, HPRS‐103 and related viruses cause predominantly myeloid leukosis (myelocytomatosis: ML) and a variety of less common tumours, with experimentally a latent period between infection and the onset of ML mortality of 9 or more weeks and a median age at death of 20 weeks. The frequency of tumours varies considerably between lines of chickens. From some cases of ML, acutely‐transforming variant viruses can be isolated which are more r...

Novel endogenous retroviral sequences in the chicken genome closely related to HPRS-103 (subgroup J) avian leukosis virus

HPRS-103, the prototype of avian leukosis virus (ALV) subgroup J, is a recently identified retrovirus associated with myeloid leukosis in meat-type chickens. Although this virus shows high sequence identity to other ALV subgroups within the gag and pol genes, its env gene is highly diverged (with only about 40% sequence identity) from other ALV subgroups. On the other hand, the sequence of the env gene of HPRS-103 was 75% identical to that of E51, a member of the EAV family of endogenous avian retroviruses. It is reported here that the chicken genome also contains another EAV-related element, EAV-HP, showing much greater sequence identity (over 97%) to the HPRS-103 env gene. Southern blotting analysis showed that EAV-HP-related sequences were distinct from EAV-O and were present in all lines of chicken examined and in grey jungle fowl, but were absent from several other avian species. The potential role of these endogenous sequences in the evolution of ALV subgroup J viruses is discussed.

The viral envelope is a major determinant for the induction of lymphoid and myeloid tumours by avian leukosis virus subgroups A and J, respectively

Among the six envelope subgroups of avian leukosis virus (ALV) that infect chickens, subgroups A (ALV-A) and J (ALV-J) are the most pathogenic and widespread among commercial chicken populations. While ALV-A is predominantly associated with lymphoid leukosis (LL) and less frequently with erythroblastosis (EB), ALV-J mainly induces tumours of the myeloid lineage. In order to examine the basis for the lineage specificity of tumour induction by these two ALV subgroups, we constructed two chimeric viruses by substituting the env genes into the reciprocal proviral clones. The chimeric HPRS-103(A) virus carrying the subgroup A env gene is identical to ALV-J prototype virus HPRS-103 except for the env gene, and the chimeric RCAS(J) virus carrying the subgroup J env gene is identical to the parent replication-competent ALV-A vector RCAS except for the env gene. In experimentally inoculated chickens, HPRS-103(A) virus induced LL and EB similar to ALV-A isolates such as RAV-1, while RCAS(J) virus induced myeloid leukosis (ML) and EB, similar to ALV-J, suggesting that the env gene is the major determinant for the lineage-specific oncogenicity. There were genetic differences in susceptibility to tumour induction between line 0 and line 15(I) chickens, indicating that in addition to the env gene, other viral or host factors could also serve as determinants for oncogenicity. Induction of both LL and ML by the two chimeric viruses occurred through the activation of c-myc, while the EB tumours were induced by activation of the c-erbB oncogene.

Acutely Transforming Avian Leukosis Virus Subgroup J Strain 966: Defective Genome Encodes a 72-Kilodalton Gag-Myc Fusion Protein

ABSTRACT Avian leukosis virus subgroup J (ALV-J), the most recent member of the avian retroviruses, is predominantly associated with myeloid leukosis in meat-type chickens. We have previously demonstrated that the acutely transforming virus strain 966, isolated from an ALV-J-induced tumor, transformed peripheral blood monocyte and bone marrow cells in vitro and induced rapid-onset tumors, suggesting transduction of oncogenes (L. N. Payne, A. M. Gillespie, and K. Howes, Avian Dis. 37:438–450, 1993). In order to understand the molecular basis for the rapid transformation and tumor induction, we have determined the complete genomic structure of the provirus of the 966 strain. The sequence of the 966 provirus clone revealed that its genome is closely related to that of HPRS-103 but is defective, with the entire pol and parts of the gag andenv genes replaced by a 1,491-bp sequence representing exons 2 and 3 of the c-myc gene. LSTC-IAH30, a stable cell line derived from turkey monocyte cultures transformed by the 966 strain of ALV-J, expressed a 72-kDa Gag-Myc fusion protein. The identification of the myc gene in 966 virus as well as in several other ALV-J-induced tumors suggested that the induction of myeloid tumors by this new subgroup of ALV occurs through mechanisms involving the activation of the c-myc oncogene.

Molecular pathogenesis of Marek's disease-recent developments.

Mareks disease (MD) is a lymphoproliferative disorder induced by a herpesvirus in chickens, its natural host. After an early cytolytic infection, the virus induces lymphomas in T-cells. These cells are latently infected with the virus, but very few viral transcripts or proteins are detectable. Although there are indications that some of these virus-encoded transcripts may be involved in tumourigenesis, the exact nature of the virus-cell interaction contributing towards the transformed phenotype is not completely understood. Among the transcripts the meq protein with basic leucine zipper (bZIP) characteristic of the fos/jun family of transcriptional activators is thought to play a major role in MDV-induced oncogenesis. Similarly the MDV-en-coded immediate early transcripts, ICP4, also seems to play an important role in latency and transformation. Apart from the virally-encoded factors, various host cell factors may be involved in the induction of tumours. Although not much work has been done in elucidating these factors, the possible role of tumour suppressor genes like p53, proto-oncogenes like Bcl-2 capable of blocking apoptosis, and telomerases in the induction of lymphomas are discussed. Some of the recent findings concerning the molecular mechanisms of interactions between MD virus and retroviruses are also presented.

Isolation of acutely transforming subgroup J avian leukosis viruses that induce erythroblastosis and myelocytomatosis

Avian leukosis virus of subgroup J (ALV-J), isolated in the late 1980s, predominantly causes myelocytic myeloid leukosis in meat-type chickens. In the past few years, we have observed the occurrence of lesions indicative of erythroblastosis in ALV-J-infected flocks and, in this paper, we report the isolation of ALV-J strains from such flocks. Three of these isolates were acutely transforming viruses, as shown by their ability to transform bone marrow cell cultures. The bone marrow cultures transformed by these virus isolates were very similar to the myeloid cells transformed by the ALV-J strain 966. However, the infection of meat-type chickens with these isolates either as embryos or as 1-day-old chicks resulted in the induction of erythroblastosis as well as myelocytomatosis. Other histopathological changes observed in the inoculated birds included neoplastic lesions such as cholangioma and testicular cell tumour, and non-neoplastic lesions such as lymphomyeloid hyperplasia. This report demonstrates that highly oncogenic ALV-J, capable of inducing a different spectrum of disease other than the widely reported myelocytomatosis, could be established in naturally infected flocks.

Tropism of subgroup J avian leukosis virus as detected by in situ hybridization

The HPRS-103 strain of avian retrovirus is the prototype of subgroup J avian leukosis virus (ALV-J) and causes myeloid leukosis in meat-type chickens. Using immunohistochemical detection of the viral groupspecific antigen (Gag) we have previously demonstrated that the induction of myeloid leukosis by ALV-J is associated with viral tropism for myelomonocytic cells. In this paper we describe an in situ hybridization (ISH) technique using digoxigenin (DIG)-labelled probes for detecting RNA transcripts in tissues from chickens infected with avian leukosis viruses (ALV) of subgroups J (HPRS-103 strain) and A (RAV-1 strain). Virus-specific RNA was detected mainly in the heart, kidney, proventriculus and adrenal in locations similar to those of the Gag protein. Viral gene expression could not be detected in the bone marrow or tumour tissues using this test. Higher levels of viral gene expression in the bursa of Fabricius infected with RAV-1, but not with HPRS-103, might help explain the inability of the latter virus to induce lymphoid leukosis.