Pathogenicity of avian leukosis viruses related to fowl glioma-inducing virus

Abstract

Fowl glioma-inducing virus (FGV), which belongs to avian leukosis virus subgroup A, causes the so-called fowl glioma and cerebellar hypoplasia in chickens. In the present study, the complete nucleotide sequences of four isolates (Tym-43, U-1, Sp-40 and Sp-53) related to the FGV prototype were determined and their pathogenicity was investigated. Phylogenetic analysis showed that the 3?-long terminal repeat of all isolates grouped together in a cluster, while sequences of the surface (SU) proteins encoded by the env gene of these viruses had 85 to 96% identity with the corresponding region of FGV. The SU regions of Tym-43, U-1 and FGV grouped together in a cluster, but those of Sp-40 and Sp-53 formed a completely separate cluster. Next, C/O specific-pathogen-free chickens were inoculated in ovo with these isolates as well as the chimeric virus RCAS(A)-(FGVenvSU), constructed by substituting the SU region of FGV into the retroviral vector RCAS(A). The four variants induced fowl glioma and cerebellar hypoplasia and the birds inoculated with Sp-53 had the most severe lesions. In contrast, RCAS(A)-(FGVenvSU) provoked only mild non-suppurative inflammation. These results suggest that the ability to induce brain lesions similar to those of the FGV prototype is still preserved in these FGV variants.

Astrocytic growth through the autocrine/paracrine production of IL-1β in the early infectious phase of fowl glioma-inducing virus

“…These mutations and insertions may affect replication efficiency of this strain. However, we confirmed that the RCAS(A) we used at this time could not induce glioma in chickens at 70 and 140 days of age (Nakamura et al, 2011).…”

“…Transformation of host cells usually takes more than 5 months in lymphoid leukosis. Although there is currently no reliable method to distinguish between reactive and neoplastic astrocytes in fowl glioma, the oncogenesis theory cannot explain the pathogenesis of fowl glioma because the gliomatous lesions are detected 35 to 70 days after in ovo infection (Nakamura et al, 2011).…”

“…Sp-53 is one of the strains that were isolated from a Japanese chicken affected with fowl glioma; this strain induced the most severe brain lesions in an experimental infection study (Nakamura et al, 2011). A replication-competent ALV-based vector, RCAS(A), was kindly donated by Dr Stephen H. Hughes (National Cancer Institute, Bethesda, MD, USA).…”

“…Phylogenic analysis of the envSU region of these variants indicated that they evolved in three clusters. In addition, FGV variants with 85 to 95% identity of envSU with FGV still have the ability to induce brain lesions, but the frequency and severity of astrocytic proliferation differ among them (Nakamura et al, 2011). However, the possibility that nodular lesions of astrocytes are directly related to the rapid and abundant replication of FGV and the variants in the brain could not be ruled out previously (Nakamura et al, 2011).…”

“…In addition, FGV variants with 85 to 95% identity of envSU with FGV still have the ability to induce brain lesions, but the frequency and severity of astrocytic proliferation differ among them (Nakamura et al, 2011). However, the possibility that nodular lesions of astrocytes are directly related to the rapid and abundant replication of FGV and the variants in the brain could not be ruled out previously (Nakamura et al, 2011). Although other retroviruses, including human immunodeficiency virus type 1 (HIV-1), human T-lymphotropic leukaemia virus and simian immunodeficiency virus, occasionally cause non-suppurative encephalitis, only limited strains of ALV-A can induce marked astrocytic growth.…”