Conserved gammaherpesvirus protein kinase selectively promotes irrelevant B cell responses

Eric J. Darrah, Christopher N. Jondle, Kaitlin E. Johnson, Gang Xin, Philip T. Lange, Weiguo Cui, Horatiu Olteanu, Vera L. Tarakanova

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Gammaherpesviruses are ubiquitous pathogens that are associated with B cell lymphomas. In the early stages of chronic infection, these viruses infect naive B cells and subsequently usurp the B cell differentiation process through the germinal center response to ensure latent infection of long-lived memory B cells. A unique feature of early gammaherpesvirus chronic infection is a robust differentiation of irrelevant, virus-nonspecific B cells with reactivities against self-antigens and antigens of other species. In contrast, protective, virus-specific humoral responses do not reach peak levels until a much later time. While several host factors are known to either promote or selectively restrict gammaherpesvirus-driven germinal center response, viral mechanisms that contribute to the irrelevant B cell response have not been defined. In this report we show that the expression and the enzymatic activity of the gammaherpesvirus-encoded conserved protein kinase selectively facilitates the irrelevant, but not virus-specific, B cell responses. Further, we show that lack of interleukin-1 (IL-1) receptor attenuates gammaherpesvirus-driven B cell differentiation and viral reactivation. Because germinal center B cells are thought to be the target of malignant transformation during gammaherpesvirus-driven lymphomagenesis, identification of host and viral factors that promote germinal center responses during gammaherpesvirus infection may offer an insight into the mechanism of gammaherpesvirus pathogenesis. IMPORTANCE Gammaherpesviruses are ubiquitous cancer-associated pathogens that usurp the B cell differentiation process to establish life-long latent infection in memory B cells. A unique feature of early gammaherpesvirus infection is the robust increase in differentiation of B cells that are not specific for viral antigens and instead encode antibodies that react with self-antigens and antigens of other species. Viral mechanisms that are involved in driving such irrelevant B cell differentiation are not known. Here, we show that gammaherpesvirus-encoded conserved protein kinase and host IL-1 signaling promote irrelevant B cell responses and gammaherpesvirus-driven germinal center responses, with the latter thought to be the target of viral transformation.

Original languageEnglish (US)
Article numberY
JournalJournal of virology
Volume93
Issue number8
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

protein kinases
Protein Kinases
B-lymphocytes
B-Lymphocytes
Germinal Center
cell differentiation
Cell Differentiation
infection
Infection
antigens
viruses
Autoantigens
interleukin-1
Viruses
Antigens
Interleukin-1 Receptors
Viral Antigens
B-Cell Lymphoma
pathogens
Virus Diseases

Keywords

  • B cell responses
  • Gammaherpesvirus
  • Germinal center
  • IL-1
  • Orf36
  • Protein kinase

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Darrah, E. J., Jondle, C. N., Johnson, K. E., Xin, G., Lange, P. T., Cui, W., ... Tarakanova, V. L. (2019). Conserved gammaherpesvirus protein kinase selectively promotes irrelevant B cell responses. Journal of virology, 93(8), [Y]. https://doi.org/10.1128/JVI.01760-18

Conserved gammaherpesvirus protein kinase selectively promotes irrelevant B cell responses. / Darrah, Eric J.; Jondle, Christopher N.; Johnson, Kaitlin E.; Xin, Gang; Lange, Philip T.; Cui, Weiguo; Olteanu, Horatiu; Tarakanova, Vera L.

In: Journal of virology, Vol. 93, No. 8, Y, 01.01.2019.

Research output: Contribution to journalArticle

Darrah, EJ, Jondle, CN, Johnson, KE, Xin, G, Lange, PT, Cui, W, Olteanu, H & Tarakanova, VL 2019, 'Conserved gammaherpesvirus protein kinase selectively promotes irrelevant B cell responses', Journal of virology, vol. 93, no. 8, Y. https://doi.org/10.1128/JVI.01760-18
Darrah, Eric J. ; Jondle, Christopher N. ; Johnson, Kaitlin E. ; Xin, Gang ; Lange, Philip T. ; Cui, Weiguo ; Olteanu, Horatiu ; Tarakanova, Vera L. / Conserved gammaherpesvirus protein kinase selectively promotes irrelevant B cell responses. In: Journal of virology. 2019 ; Vol. 93, No. 8.
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