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Macrophages drive KSHV B cell latency

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Resumo:Kaposi's sarcoma herpesvirus (KSHV) establishes lifelong infection and persists in latently infected B cells. Paradoxically, in vitro B cell infection is inefficient, and cells rapidly die, suggesting the absence of necessary factor(s). KSHV epidemiology unexpectedly mirrors that of malaria and certain helminthic infections, while other herpesviruses are ubiquitous. Elevated circulating monocytes are common in these parasitic infections. Here, we show that KSHV infection of monocytes or M-CSF-differentiated (M2) macrophages is highly efficient. Proteomic analyses demonstrate that infection induces macrophage production of B cell chemoattractants and activating factor. We find that KSHV acts with monocytes or M2 macrophages to stimulate B cell survival, proliferation, and plasmablast differentiation. Further, macrophages drive infected plasma cell differentiation and long-term viral latency. In Kenya, where KSHV is endemic, we find elevated monocyte levels in children with malaria. These findings demonstrate a role for mononuclear phagocytes in KSHV B cell latency and suggest that mononuclear phagocyte abundance may underlie KSHV's geographic disparity.
Autores principais:Szymula, Agnieszka
Outros Autores:Samayoa-Reyes, Gabriela; Ogolla, Sidney; Liu, Bing; Li, Shijun; George, Athira; Sciver, Nicholas Van; Rochford, Rosemary; Simas, J. Pedro; Kaye, Kenneth M.
Assunto:B cell CP: Immunology Kaposi's sarcoma-associated herpesvirus KSHV latent infection Macrophage Malaria Monocyte Plasma cell
Ano:2023
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade Católica Portuguesa
Idioma:inglês
Origem:Veritati - Repositório Institucional da Universidade Católica Portuguesa

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