Chicken Anemia Virus

Schat, Karel A.

doi:10.1007/978-3-540-70972-5_10

Cited by 90 publications

(84 citation statements)

References 120 publications

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“…It is likely that during early stages of viral infection in normal (nontransformed) host cells, apoptin remains cytoplasmic and inactive. During rolling-circle replication of the CAV genome, single-stranded DNA is generated and serves as a trigger for DNA damage sensors, including RPA and other components involved in ATR activation (3). Abnormal replication fork structures subsequently generate double-strand breaks (DSB) and induce recruitment and activation of ATM (25,26).…”

Section: Discussionmentioning

confidence: 99%

“…In particular, chicken anemia virus (CAV), a member of the genus Gyrovirus, is the etiological agent of chicken infectious anemia. CAV infects several bone marrow-derived cells, resulting in severe anemia and immunosuppression in young chickens and compromised immune response in older birds (3,4). CAV can lead to considerable economic loss during intensive chicken farming, and control of the virus through vaccination is currently standard practice.…”

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confidence: 99%

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Activation of the Chicken Anemia Virus Apoptin Protein by Chk1/2 Phosphorylation Is Required for Apoptotic Activity and Efficient Viral Replication

Kucharski

Sharon

et al. 2016

J Virol

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Chicken anemia virus (CAV) is a single-stranded circular DNA virus that carries 3 genes, the most studied of which is the gene encoding VP3, also known as apoptin. This protein has been demonstrated to specifically kill transformed cells while leaving normal cells unharmed in a manner that is independent of p53 status. Although the mechanistic basis for this differential activity is unclear, it is evident that the subcellular localization of the protein is important for the difference. In normal cells, apoptin exists in filamentous networks in the cytoplasm, whereas in transformed cells, apoptin is present in the nucleus and appears as distinct foci. We have previously demonstrated that DNA damage signaling through the ataxia telangiectasia mutated (ATM) pathway induces the translocation of apoptin from the cytoplasm to the nucleus, where it induces apoptosis. We found that apoptin contains four checkpoint kinase consensus sites and that mutation of either threonine 56 or 61 to alanine restricts apoptin to the cytoplasm. Furthermore, treatment of tumor cells expressing apoptin with inhibitors of checkpoint kinase 1 (Chk1) and Chk2 causes apoptin to localize to the cytoplasm. Importantly, silencing of Chk2 rescues cancer cells from the cytotoxic effects of apoptin. Finally, treatment of virus-producing cells with Chk inhibitor protects them from virus-mediated toxicity and reduces the titer of progeny virus. Taken together, our results indicate that apoptin is a sensor of DNA damage signaling through the ATM-Chk2 pathway, which induces it to migrate to the nucleus during viral replication. IMPORTANCEThe chicken anemia virus (CAV) protein apoptin is known to induce tumor cell-specific death when expressed. Therefore, understanding its regulation and mechanism of action could provide new insights into tumor cell biology. We have determined that checkpoint kinase 1 and 2 signaling is important for apoptin regulation and is a likely feature of both tumor cells and host cells producing virus progeny. Inhibition of checkpoint signaling prevents apoptin toxicity in tumor cells and attenuates CAV replication, suggesting it may be a future target for antiviral therapy. Circoviruses are a diverse group of nonenveloped, icosahedral viruses containing circular, single-stranded DNA genomes (1, 2). These viruses have been shown to infect a wide range of hosts, and they are the causative agents of several serious diseases in animals. In particular, chicken anemia virus (CAV), a member of the genus Gyrovirus, is the etiological agent of chicken infectious anemia. CAV infects several bone marrow-derived cells, resulting in severe anemia and immunosuppression in young chickens and compromised immune response in older birds (3, 4). CAV can lead to considerable economic loss during intensive chicken farming, and control of the virus through vaccination is currently standard practice. Recently, a novel circovirus with partial homology to CAV isolated from a skin swab was designated human gyrovirus (HGyV) (5). The identificati...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Activation of the Chicken Anemia Virus Apoptin Protein by Chk1/2 Phosphorylation Is Required for Apoptotic Activity and Efficient Viral Replication

Kucharski

Sharon

et al. 2016

J Virol

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“…The clinical disease is characterized by poor weight gain, aplastic anaemia, subcutaneous and muscular haemorrhages, generalized lymphoid atrophy and immunosuppression (McNulty et al, 1991;Adair, 2000;Miller and Schat, 2004;Schat, 2009;Todd, 2000;Dhama et al, 2008). However, subclinical infections characterized by production losses and vaccine associated complications can act as source of infection to other flocks (McNulty et al, 1991;Dhama et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Immunosuppressive Effects of Chicken Infectious Anaemia Virus on T Lymphocyte Populations Using Flow Cytometry and Hematological Parameters During Experimental Subclinical Infection in Chicks

Wani¹

2015

Adv. Anim. Vet. Sci.

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| Chicken infectious anaemia virus (CIAV) is an economically important pathogen affect-ing poultry industry worldwide, and renders birds susceptible to secondary infections. The present study was designed to investigate the systemic immunosuppressive effects of CIAV on T lymphocytes bearing CD4 and CD8 receptors using flow cytometry and hematological parameters during experimental subclinical infection in chicks. Forty specific pathogen free (SPF) chicks of 6 weeks of age were randomly and equally divided into two groups. Infected group received 10 4.5 TCID 50 of CIAV while control chicks were mock inoculated. All the chicks were regularly monitored for clinical signs, hematology parameters and CD4 + and CD8 + cell populations in spleen and blood. The experimental CIAV infection was confirmed by PCR testing of the tissue samples of experimental chicks, using VP2 gene specific primers, which yielded an expected amplicon size of 651 base pairs. The analysis of the hematological parameters showed significant decline in hematocrit value (PCV), total leukocyte count (TLC) and peripheral lymphocyte count (PLC) after 15 days post infection (dpi) but with no clinical signs of CIA. Flow cytometric analysis revealed that the percentage of CD4 + CD8 -and CD4 -CD8 + T cells significantly decreased in the virus infected chicks at 15 dpi both in the spleen and blood (p<0.05). The results supported the fact that subclinical CIAV infections are also immunodepressive in nature; the virus replicates in primary lymphoid tissues and induces immunosuppression by decreasing both CD4 + and CD8 + T cells in chicks.

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“…CAV has been the only known species of the Gyrovirus genus, which is part of the family Circoviridae. CAV is a nonenveloped virus, with an icosahedral capsid 19 to 27 nm in diameter surrounding a single-stranded (ss) circular genomic DNA (8). In a skin swab taken from a healthy person, we discovered a new human virus that we have designated human gyrovirus (HGyV) because of its homology with the chicken anemia virus.…”

mentioning

confidence: 99%

Identification of the First Human Gyrovirus, a Virus Related to Chicken Anemia Virus

Sauvage

Cheval²,

Foulongne

et al. 2011

J Virol

102

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We have identified in a skin swab sample from a healthy donor a new virus that we have named human gyrovirus (HGyV) because of its similarity to the chicken anemia virus (CAV), the only previously known member of the Gyrovirus genus. In particular, this virus encodes a homolog of the CAV apoptin, a protein that selectively induces apoptosis in cancer cells. By PCR screening, HGyV was found in 5 of 115 other nonlesional skin specimens but in 0 of 92 bronchoalveolar lavages or nasopharyngeal aspirates and in 0 of 92 fecal samples.

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Chicken Anemia Virus

Cited by 90 publications

References 120 publications

Activation of the Chicken Anemia Virus Apoptin Protein by Chk1/2 Phosphorylation Is Required for Apoptotic Activity and Efficient Viral Replication

Activation of the Chicken Anemia Virus Apoptin Protein by Chk1/2 Phosphorylation Is Required for Apoptotic Activity and Efficient Viral Replication

Immunosuppressive Effects of Chicken Infectious Anaemia Virus on T Lymphocyte Populations Using Flow Cytometry and Hematological Parameters During Experimental Subclinical Infection in Chicks

Identification of the First Human Gyrovirus, a Virus Related to Chicken Anemia Virus

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