+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Murine gammaherpesvirus M2 protein induction of IRF4 via the NFAT pathway leads to IL-10 expression in B cells

, : Murine gammaherpesvirus M2 protein induction of IRF4 via the NFAT pathway leads to IL-10 expression in B cells. Plos Pathogens 10(1): E1003858-E1003858

Reactivation of the gammaherpesviruses Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus 68 (MHV68) from latently infected B cells has been linked to plasma cell differentiation. We have previously shown that the MHV68 M2 protein is important for virus reactivation from B cells and, when expressed alone in primary murine B cells, can drive B cell differentiation towards a pre-plasma cell phenotype. In addition, expression of M2 in primary murine B cells leads to secretion of high levels of IL-10 along with enhanced proliferation and survival. Furthermore, the absence of M2 in vivo leads to a defect in the appearance of MHV68 infected plasma cells in the spleen at the peak of MHV68 latency. Here, employing an inducible B cell expression system, we have determined that M2 activates the NFAT pathway in a Src kinase-dependent manner--leading to induction of the plasma cell-associated transcription factor, Interferon Regulatory Factor-4 (IRF4). Furthermore, we show that expression of IRF4 alone in a B cell line up-regulates IL-10 expression in culture supernatants, revealing a novel role for IRF4 in B cell induced IL-10. Consistent with the latter observation, we show that IRF4 can regulate the IL-10 promoter in B cells. In primary murine B cells, addition of cyclosporine (CsA) resulted in a significant decrease in M2-induced IL-10 levels as well as IRF4 expression, emphasizing the importance of the NFAT pathway in M2- -mediated induction of IL-10. Together, these studies argue in favor of a model wherein M2 activation of the NFAT pathway initiates events leading to increased levels of IRF4--a key player in plasma cell differentiation--which in turn triggers IL-10 expression. In the context of previous findings, the data presented here provides insights into how M2 facilitates plasma cell differentiation and subsequent virus reactivation.


PMID: 24391506

DOI: 10.1371/journal.ppat.1003858

Other references

Kovacev, M.; Durdević, L.J.; Gavanski, K., 1967: Rehabilitation and working capacity of women treated for malignant tumors of the genitalia. Medicinski Pregled 20(1): 91-94

Sarvesan, R., 1976: On the occurrence of sepia trygonina cephalopoda sepiidae in gulf of mannar india. The occurrence of the cuttlefish, S. trygonina (Rochebrune), in Indian waters is confirmed. A brief description of the species based on specimens of 1 male and 1 female collected from Gulf of Mannar off Tuticorin [India] is given.

Kawamura, H.; Taguchi, K.; Hirata, Y., 2002: Automatic deodorizing system for waste water from radioisotope facilities using an ozone generator. We applied an ozone generator to sterilize and to deodorize the waste water from radioisotope facilities. A small tank connected to the generator is placed outside of the drainage facility founded previously, not to oxidize the other apparatus, Th...

Fajardo, B., 2001: Life-threatening illness in the analyst. The literature on practicing throughout a life-threatening illness is reviewed and important differences about attitudes toward self-disclosure are understood by noting a division between two perspectives on transference: "one-body" and...

Bouma, J.; Laat, P.J.M. de; Holst, A.F.V.n, 1981: Use of soil-survey data for hydrological simulation models. Existing soil-survey data, such as soil texture, structure, bulk density, organic matter content and horizon designations provides a satisfactory source for deriving basic soil data for computer simulation of soil-moisture regimes and associated c...

Bateson, P.P.; Seaburne-May, G., 1973: Effects of prior exposure to light on chicks' behaviour in the imprinting situation. Day-old domestic chicks previously exposed to a constant light approached a flashing rotating light more rapidly than chicks previously kept in darkness. The speed of approach was inversely related to the length of exposure, and effects were appar...

Elberg, S.S.; Fong, J.; Schneider, P., 1956: Studies on tubercle bacillus-monocyte relationship. I. Quantitative analysis of effect of serum of animals vaccinated with BCG upon bacterium-monocyte system. Studies on cultivation of rabbit monocytes in vitro have shown that preliminary trypsinization of cells followed by cultivation in 40% normal or immune rabbit serum in Tyrodes solution afforded optimal conditions for maintenance of constant cell p...

Tuttle, T.; Habermann, E.; Abraham, A.; Emory, T.; Virnig, B., 2007: Contralateral prophylactic mastectomy for patients with unilateral breast cancer. Patients with unilateral breast cancer are at increased risk of developing a second cancer in the contralateral breast. Some women choose contralateral prophylactic mastectomy (CPM) to prevent cancer in the contralateral breast. Several studies ha...

Caldwell, K., 1997: Ideological influences on curriculum development in nurse education. The development of curricula in nurse education cannot be viewed in isolation from the socio-political context within which it exists. Changes in the prevailing political ideology have impacted on the social life of individuals, and the reflection...

Bogacz W., 1991: Tectogenetic aspects of deformation and mineralization in the Western Australian cratonic environment. Publication - Geology Department and Extension Service, University of Western Australia 25: 108-111