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A Common Live-Attenuated Avian Herpesvirus Vaccine Expresses a Very Potent Oncogene.

ABSTRACT: Vaccines play a crucial role in the protection of animals and humans from deadly pathogens. The first vaccine that also protected against cancer was developed against the highly oncogenic herpesvirus Marek's disease virus (MDV). MDV infects chickens and causes severe immunosuppression, neurological signs, and fatal lymphomas, a process that requires the viral oncogene, meq The most frequently used Marek's disease vaccine is the live-attenuated CVI988/Rispens (CVI) strain, which efficiently protects chickens and prevents tumorigenesis. Intriguingly, CVI expresses at least two isoforms of meq; however, it remains unknown to what extent these isoforms contribute to virus attenuation. In this study, we individually examined the contribution of the two CVI-meq isoforms to the attenuation of the vaccine. We inserted the respective isoforms into a very virulent MDV (strain RB-1B), thereby replacing its original meq gene. Surprisingly, we could demonstrate that the longer isoform of meq strongly enhanced virus-induced pathogenesis and tumorigenesis, indicating that other mutations in the CVI genome contribute to virus attenuation. On the contrary, the shorter isoform completely abrogated pathogenesis, demonstrating that changes in the meq gene can indeed play a key role in virus attenuation. Taken together, our study provides important evidence on attenuation of one of the most frequently used veterinary vaccines worldwide.IMPORTANCE Marek's disease virus (MDV) is one of several oncogenic herpesviruses and causes fatal lymphomas in chickens. The current "gold standard" vaccine is the live-attenuated MDV strain CVI988/Rispens (CVI), which is widely used and efficiently prevents tumor formation. Intriguingly, CVI expresses two predominant isoforms of the major MDV oncogene meq: one variant with a regular size of meq (Smeq) and one long isoform (Lmeq) harboring an insertion of 180 bp in the transactivation domain. In our study, we could break the long-standing assumption that the Lmeq isoform is an indicator for virus attenuation. Using recombinant viruses that express the different CVI-meq isoforms, we could demonstrate that both isoforms drastically differ in their abilities to promote pathogenesis and tumor formation in infected chickens.

SUBMITTER: Conradie AM

PROVIDER: S-EPMC6796977 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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A Common Live-Attenuated Avian Herpesvirus Vaccine Expresses a Very Potent Oncogene.

Conradie Andelé M AM Bertzbach Luca D LD Bhandari Nirajan N Parcells Mark M Kaufer Benedikt B BB

mSphere 20191009 5

Vaccines play a crucial role in the protection of animals and humans from deadly pathogens. The first vaccine that also protected against cancer was developed against the highly oncogenic herpesvirus Marek's disease virus (MDV). MDV infects chickens and causes severe immunosuppression, neurological signs, and fatal lymphomas, a process that requires the viral oncogene, <i>meq</i> The most frequently used Marek's disease vaccine is the live-attenuated CVI988/Rispens (CVI) strain, which efficientl ...[more]

PMID: 31597721

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Project description:In this study, the protective efficacy of an E. coli live attenuated vaccine was compared to the preventive administration of lectin preparation before the challenge. Two hundred broiler chicks were divided into eight equal groups. The first group was used as a negative control group. Three groups were vaccinated at day 1 with the avian colibacillosis live vaccine of which one group served as a vaccinated nonchallenged group. Another two groups were treated with lectin product (0.5 mL/L drinking water) for three days before the challenge. The last two groups served as challenge control for either E. coli O78 or O125 strains. The challenge was conducted at three weeks of age with either homologous O78 or heterologous O125 E. coli strains, using 0.5 mL/bird of each avian pathogenic E. coli (APEC) strain (~108 colony forming units "CFU"/mL)/subcutaneously. The bodyweight and feed conversion ratios (FCR) were calculated for four weeks. Clinical signs and gross and histopathological lesions were scored at two and seven days post inoculation (dpi). The heart and liver of euthanized chickens at 2 dpi were removed aseptically and homogenized to evaluate pathogenic E. coli colonization. Results showed that live avian colibacillosis vaccine reduced mortalities and APEC colonization in the homologous challenge group but not in the heterologous challenge group. Lectin-treated groups showed 20% and 16% mortality after challenge with E. coli O78 and O125, respectively, and both groups showed performance parameters, clinical signs, and histopathological lesion scores comparable to the negative control group, with variable E. coli colonization of heart and liver. The study demonstrated the efficacy of live attenuated avian colibacillosis vaccine against homologous but not heterologous APEC challenge in broiler chickens. The lectin-containing products can be used as a preventive medication to reduce the clinical impacts of colibacillosis regardless of the challenge strain. Standardization of the evaluation parameters for APEC vaccines is recommended.

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A Common Live-Attenuated Avian Herpesvirus Vaccine Expresses a Very Potent Oncogene.

Publications

A Common Live-Attenuated Avian Herpesvirus Vaccine Expresses a Very Potent Oncogene.

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