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Depression of Vaccinal Immunity to Marek's Disease by Infection with Chicken Infectious Anemia Virus.

ABSTRACT: Marek's disease (MD) has been occurring with increasing frequency in chickens in recent years. To our knowledge, however, there has been no report of the very virulent plus (vv+) MD virus (MDV) field isolate in China. Studies have shown that dual infection with immunosuppressive viruses such as chicken infectious anemia virus (CIAV) occurs frequently in chickens developing MD. In this study, we performed a designed set of in vivo experiments, which comprised five different groups of chickens, including the group of CVI988/Rispens-vaccinated chickens, the groups of CVI988/Rispens-vaccinated chickens infected with MDV or CIAV or both viruses (MDV and CIAV), and the group of MDV-challenged chickens. The effects of CIAV dual infection on the immunization of commercial MDV vaccine CVI988/Rispens were evaluated. The results show that infection of the SD15 strain of CIAV significantly reduced the weight and antibody titers to avian influenza virus (AIV)/Newcastle disease virus (NDV) inactivated vaccines of chickens immunized with the CVI988/Rispens, and resulted in the atrophy of thymus/bursa and the enlargement of spleen. The CVI988/Rispens vaccination conferred good immune protection for chickens challenged with 2000 PFU of the GX0101 strain of MDV. However, dual infection with SD15 significantly reduced the body weight, antibody titers induced by AIV/NDV inactivated vaccines and protective index of CVI988/Rispens, and resulted in the aggravation of the immunosuppression, mortality, and viremia of GX0101 in CVI988/Rispens-immunized/GX0101-challenged chickens. Overall, CIAV infection significantly reduced the protective effects of the CVI988/Rispens vaccine against MDV, implying that concurrent infection with CIAV may be a major contributor in the frequent attacks of MD in China in recent years.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC5622928 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The objective of the present study was to determine if chicken melanoma differentiation-associated gene 5 (MDA5) senses infectious bursal disease virus (IBDV) infection to initiate and amplify an innate immune response in the chicken MDA5 (chMDA5) signaling pathway. Chicken embryo fibroblast DF-1 cells were infected with IBDV LP1 at a multiplicity of infection (MOI) of 0.5 or 10. In addition, knockdown and overexpression of chMDA5 were performed by transfecting DF-1 cells with chMDA5-targeting small interfering RNA (siRNA) or chMDA5-expressing DNA. The transfected cells were infected with IBDV LP1 at an MOI of 10. Cell culture supernatants and lysates were collected at 2, 8, 16 and 24 hours postinfection (hpi) for IBDV titer determination and RNA extraction, respectively. IBDV RNA loads and mRNA expression levels of chicken MDA5, interferon-? (IFN-?) promoter stimulator 1 (IPS-1), interferon regulatory factor-3 (IRF-3), IFN-?, double-stranded RNA-dependent protein kinase (PKR), 2',5'-oligoadenylate synthetase (OAS), myxovirus resistance gene (Mx), and major histocompatibility complex class I (MHC class I) were determined by real-time RT-PCR. The IBDV titer increased up to 1.4 × 10(7) plaque-forming units (PFU)/mL at 24 hpi, and the IBDV RNA load reached 464 ng/?L at 24 hpi. The mRNA expression levels of chicken MDA5, IRF-3, IFN-?, PKR, OAS, Mx and MHC class I in IBDV-infected DF-1 cells exhibited significant (p < 0.05) upregulation up to 906-, 199-, 26,310-, 12-, 66,144-, 64,039- and 33-fold, respectively. Expressed chMDA5 from transfection and double-stranded RNA from IBDV infection were localized or colocalized in the cytoplasm of DF-1 cells at 16 hpi. When chMDA5 was knocked down in DF-1 cells, IBDV titers and RNA loads were significantly higher (p < 0.05) than those in DF-1 cells without chMDA5 knockdown at 24 hpi. The expression levels of chicken MDA5, IRF-3, IFN-? and MHC class I in chMDA5-knockdown DF-1 cells were significantly lower (p < 0.05) at 16 and 24 hpi. DF-1 cells overexpressing chMDA5 by transfection with chMDA5 expressing DNA had significantly lower (p < 0.05) IBDV titers and RNA loads at 16 and 24 hpi and showed significantly higher (p < 0.05) expression of chicken MDA5, IRF-3, IFN-?, PKR, OAS, Mx and MHC class I at 2 hpi. The results indicated that chicken MDA5 recognized IBDV infection and that this interaction resulted in the activation of chMDA5-related innate immune genes and upregulation of chicken MHC class I.

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Depression of Vaccinal Immunity to Marek's Disease by Infection with Chicken Infectious Anemia Virus.

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