Kinetic analysis of pathogenicity and tissue tropism of gyrovirus 3 in experimentally infected chickens.

Gyrovirus 3 (GyV3), the third novel emerging species of the genus Gyrovirus of the Anelloviridae family, has been described in multiple hosts. Epidemiologically, there are suggestions that GyV3 is associated with diarrhea/proventriculitis, however, no direct causal evidence exists between GyV3 infection and specific clinical diseases. Herein, we infected special pathogen-free (SPF) chickens with GyV3, and then assessed the pathogenicity and tissue tropism. The results revealed that GyV3 induced persistent infection characterized by diarrhea, aplastic anemia, immunosuppression, and persistent systemic lymphocytic inflammation. Clinically, the infected chickens presented ruffled feathers, diarrhea, anemia, and weight loss. Aplastic anemia was characterized by progressive depletion of hematopoietic cells in the bone marrow, immunosuppression was associated with atrophy of the thymus, spleen, and bursa of Fabricious, progressive lymphocytic inflammations were characterized by proventriculitis, adrenalitis, pancreatitis, hepatitis, nephritis, and bronchitis. Viral loads of GyV3 in tissues exhibited "M", "N", "W" or "V" type dynamic changes. The highest level of viral loads was reported in bone marrow at 7dpi, followed by the adrenal gland at 2 dpi, the sciatic nerve at 7 dpi, and bile at 35 dpi. The bone marrow and kidney demonstrate the strongest immunostaining of GyV3-VP1 antigen and were suggested as the target tissues of GyV3. Collectively, GyV3 is an immunosuppressive pathogenic virus that targets the bone marrow and kidney in chickens. Exploring the pathogenicity and tissue tropism of GyV3 will guide the basic understanding of the biology of GyV3 and its pathogenesis in chickens.

Cross-species pathogenicity of gyrovirus 3 in experimentally infected chickens and mice.

Gyrovirus 3 (GyV3) has been identified in humans and other hosts, suggesting its cross-species pathogenicity, which poses an increased public health risk. In the current study, we established chicken and mouse models of GyV3 infection. We found that GyV3 induced persistent infections, characterized by viremia, aplastic anemia, immunosuppression, and systematic lymphocytic inflammation, in both species. Kinetic viral loads and antigen expression demonstrated rapid viral replication and broad tissue tropism of GyV3 in both models. The highest viral loads and the strongest antigen immunostaining were present in bone marrow and cerebrum in both chickens and mice, indicating that these are target tissues for GyV3. Genetic diversity analysis of VP1 in infected chickens and mice showed that GyV3 adapts to new hosts via rapid evolution of the hypervariable region of the gene encoding the structural protein VP1. Overall, our results indicate that GyV3 is a cross-species pathogenic virus; therefore, more attention needs to be paid to high levels of GyV3-induced neurotropism and aplastic anemia as a public health risk.

Severe neurologic disease and chick mortality in crested screamers (Chauna torquata) infected with a novel Gyrovirus.

Gyroviruses are small, single stranded DNA viruses in the family Anelloviridae. In chickens, the type virus (chicken anemia virus; CAV) causes epidemic disease in poultry flocks worldwide. In 2007 and 2008, young crested screamers (Chauna torquata) at a zoo in Wisconsin, USA, died of neurologic disease with clinical and pathological features resembling CAV infection. Conventional diagnostics were negative, but molecular analyses revealed coinfection of an affected bird with three variants of a novel Gyrovirus lineage, GyV10. Analysis of ten additional screamers from this and another zoo revealed infection in all but one bird, with co-infections and persistent infections common. The association between GyV10 ("screamer anemia virus," provisionally) and the disease remains unproven, but certain immunological and neurologic features of the syndrome would expand the known pathologic consequences of Gyrovirus infection. To control the virus, autogenous vaccines, environmental decontamination, and management strategies to limit vertical and horizontal transmission might prove effective.