Kaposi's Sarcoma-Associated Herpesvirus Latency Locus Renders B Cells Hyperresponsive to Secondary Infections
Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV) induces B cell hyperplasia and neoplasia, such as multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL). To explore KSHV-induced B cell reprogramming in vivo, we expressed the KSHV latency locus, inclusive of all viral microRNAs (miRNAs), in B cells of transgenic mice in the absence of the inhibitory FcγRIIB receptor. The BALB/c strain was chosen as this is the preferred model to study B cell differentiation. The mice developed hyperglobulinemia, plasmacytosis, and B lymphoid hyperplasia. This phenotype was ameliorated by everolimus, which is a rapamycin derivative used for the treatment of mantle cell lymphoma. KSHV latency mice exhibited hyperresponsiveness to the T-dependent (TD) antigen mimic anti-CD40 and increased incidence of pristane-induced inflammation. Lastly, the adaptive immunity against a secondary infection with Zika virus (ZIKV) was markedly enhanced. These phenotypes are consistent with KSHV lowering the activation threshold of latently infected B cells, which may be beneficial in areas of endemicity, where KSHV is acquired in childhood and infections are common.IMPORTANCE Kaposi's sarcoma-associated herpesvirus (KSHV) establishes latency in B ...Continue Reading
References
Induction of lupus-associated autoantibodies in BALB/c mice by intraperitoneal injection of pristane
Citations
Related Concepts
Related Feeds
Antivirals
Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.
Antivirals (ASM)
Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.
Castleman Disease
Castleman disease is a rare disorder that involves an overgrowth of cells in the lymph nodes. Unicentric Castleman disease affects one lymph node, usually in the chest or abdomen. Multicentric Castleman disease affects multiple lymph nodes, commonly located in the neck, collarbone, underarm and groin areas. Discover the latest research on Castleman disease here.
B cell Differentiation
Depending on the signal received through the B cell receptor and other receptors, B cells differentiate into follicular or marginal zone B cells. Here is the latest research pertaining to this differentiation process.