Interindividual Spread of Herpesviruses

Jarosinski, Keith W.

doi:10.1007/978-3-319-53168-7_9

Cited by 17 publications

(19 citation statements)

References 129 publications

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“…In these different cell types, MDV remains cell-associated and is spread by cell-to-cell transmission. However, from around 10 days after infection, the infection is transferred to the feather follicle epithelial cells, the unique cell type from where the cell-free infectious virus is shed into the poultry house environment for long periods of time, acting as a source of infection to naïve newly introduced birds (Jarosinski, 2017). Thus, MDV shows infection of different types of cells with distinct virus-host interactions and outcomes.…”

Section: Pathogenesismentioning

confidence: 99%

Spotlight on avian pathology: Marek’s disease

Nair

2018

Avian Pathology

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Marek's disease (MD), characterised by rapid-onset lymphoid tumours, immunosuppression and paralysis, is one of the most widespread economically important diseases of poultry world-wide. Caused by the highly contagious Marek's disease virus, control of MD is mainly achieved through vaccination with live attenuated vaccines, although improvements in genetic resistance have also been an important component of disease control. Despite the overall success of the vaccination policy in controlling MD in the last 40 years, continuous evolution of virulence and emergence of hypervirulent pathotypes remains the major challenge for sustainable control of this disease.

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Section: Pathogenesismentioning

confidence: 99%

Spotlight on avian pathology: Marek’s disease

Nair

2018

Avian Pathology

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“…As with other herpesviruses studied, MDV CHPK, encoded by the UL13 gene, is not essential for cell-to-cell spread in tissue culture cells. In chickens, MDV CHPK is dispensable for replication, latency, and reactivation in T cells but is required for interindividual spread, implicating a critical role for this kinase during natural infection (48,49,52,53).…”

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confidence: 99%

Expression of the Conserved Herpesvirus Protein Kinase (CHPK) of Marek’s Disease Alphaherpesvirus in the Skin Reveals a Mechanistic Importance for CHPK during Interindividual Spread in Chickens

Krieter

Ponnuraj

Jarosinski

2020

J Virol

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The Herpesviridae encode many conserved genes, including the conserved herpesvirus protein kinase (CHPK) that has multifunctional properties. In most cases, herpesviruses lacking CHPK can propagate in cell culture to various degrees, depending on the virus and cell culture system. However, in the natural animal model system of Marek’s disease alphaherpesvirus (MDV) in chickens, CHPK is absolutely required for interindividual spread from chicken to chicken. The lack of biological reagents for chicken and MDV has limited our understanding of this important gene during interindividual spread. Here, we engineered epitope-tagged proteins in the context of virus infection in order to detect CHPK in the host. Using immunofluorescence assays and Western blotting during infection in cell culture and in chickens, we determined that the invariant lysine 170 (K170) of MDV CHPK is required for interindividual spread and autophosphorylation of CHPK and that mutation to methionine (M170) results in instability of the CHPK protein. Using these newly generated viruses allowed us to examine the expression of CHPK in infected chickens, and these results showed that mutant CHPK localization and late viral protein expression were severely affected in feather follicles wherein MDV is shed, providing important information on the requirement of CHPK for interindividual spread. IMPORTANCE Marek’s disease in chickens is caused by Gallid alphaherpesvirus 2, better known as Marek’s disease alphaherpesvirus (MDV). Current vaccines only reduce tumor formation but do not block interindividual spread from chicken to chicken. Understanding MDV interindividual spread provides important information for the development of potential therapies to protect against Marek’s disease while also providing a reliable natural host in order to study herpesvirus replication and pathogenesis in animals. Here, we studied the conserved Herpesviridae protein kinase (CHPK) in cell culture and during infection in chickens. We determined that MDV CHPK is not required for cell-to-cell spread, for disease induction, and for oncogenicity. However, it is required for interindividual spread, and mutation of the invariant lysine (K170) results in stability issues and aberrant expression in chickens. This study is important because it addresses the critical role CHPK orthologs play in the natural host.

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“…One of the objectives of our laboratory is to identify herpesviral genes required for replication and host-to-host transmission that could be targeted in blocking the spread of herpesviruses in a population. Current vaccines against MD do not block chickento-chicken transmission of MDV, resulting in increased MD virulence over the decades (20,21). Cell culture propagation of MDV does not result in the production of infectious cell-free virus, relying exclusively on cell-to-cell spread (22)(23)(24), while fully infectious virus is produced in FFE cells of the skin (25).…”

mentioning

confidence: 99%

“…Cell culture propagation of MDV does not result in the production of infectious cell-free virus, relying exclusively on cell-to-cell spread (22)(23)(24), while fully infectious virus is produced in FFE cells of the skin (25). The generation of infectious cell-free virus is believed to be required for interindividual spread from chicken to chicken (20). Very little is known about the maturation of MD viral particles in cell culture and the shedding of infectious virus from FFE cells.…”

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confidence: 99%

TheHerpesviridaeConserved Multifunctional Infected-Cell Protein 27 (ICP27) Is Important but Not Required for Replication and Oncogenicity of Marek’s Disease Alphaherpesvirus

Ponnuraj

Tien

Vega-Rodriguez

et al. 2019

J Virol

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The Herpesviridae conserved infected-cell protein 27 (ICP27) is essential for cell culture-based replication of most herpesviruses studied. For members of the Alphaherpesvirinae, ICP27 regulates the expression of many viral genes, including expression of pUL44 (gC), pUL47 (VP13/14), and pUL48 (VP16). These three viral proteins are dysregulated during Marek’s disease alphaherpesvirus (MDV) replication in cell culture. MDV replicates in a highly cell-associated manner in cell culture, producing little to no infectious virus. In contrast, infectious cell-free MDV is produced in specialized feather follicle epithelial (FFE) cells of infected chickens, in which these three genes are abundantly expressed. This led us to hypothesize that MDV ICP27, encoded by gene UL54, is a defining factor for the dysregulation of gC, pUL47, and pUL48 and, ultimately, ineffective virus production in cell culture. To address ICP27’s role in MDV replication, we generated recombinant MDV with ICP27 deleted (vΔ54). Interestingly, vΔ54 replicated, but plaque sizes were significantly reduced compared to those of parental viruses. The reduced cell-to-cell spread was due to ICP27 since plaque sizes were restored in rescued viruses, as well as when vΔ54 was propagated in cells expressing ICP27 in trans. In chickens, vΔ54 replicated, induced disease, and was oncogenic but was unable to transmit from chicken to chicken. To our knowledge, this is the first report showing that the Herpesviridae conserved ICP27 protein is dispensable for replication and disease induction in its natural host. IMPORTANCE Marek’s disease (MD) is a devastating oncogenic disease that affects the poultry industry and is caused by MD alphaherpesvirus (MDV). Current vaccines block induction of disease but do not block chicken-to-chicken transmission. There is a knowledge gap in our understanding of how MDV spreads from chicken to chicken. We studied the Herpesviridae conserved ICP27 regulatory protein in cell culture and during MDV infection in chickens. We determined that MDV ICP27 is important but not required for replication in both cell culture and chickens. In addition, MDV ICP27 was not required for disease induction or oncogenicity but was required for chicken-to-chicken transmission. This study is important because it addresses the role of ICP27 during infection in the natural host and provides important information for the development of therapies to protect chickens against MD.

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Interindividual Spread of Herpesviruses

Cited by 17 publications

References 129 publications

Spotlight on avian pathology: Marek’s disease

Spotlight on avian pathology: Marek’s disease

Expression of the Conserved Herpesvirus Protein Kinase (CHPK) of Marek’s Disease Alphaherpesvirus in the Skin Reveals a Mechanistic Importance for CHPK during Interindividual Spread in Chickens

TheHerpesviridaeConserved Multifunctional Infected-Cell Protein 27 (ICP27) Is Important but Not Required for Replication and Oncogenicity of Marek’s Disease Alphaherpesvirus

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