Impaired Control of Chronic Herpesvirus Infection in Tissue Resident Macrophages During Coinfection with Intestinal Parasite and Other Cell-intrinsic Herpesvirus Interactions

Gammaherpesviruses are chronic pathogens that infect lymphocytes, such as B cells, dendritic cells, and macrophages. Reactivation of gammaherpesviruses is thought to induce lymphomas and can be caused by a variety of signals, such as HDAC inhibitors. While some of these signals are known, it is still unclear whether there are cell-specific reactivation mechanisms, and if so, which signals cause them. Further, human gammaherpesviruses are endemic in areas that also have a high prevalence of helminth infections. Coinfection with parasites has been shown to induce murine gammaherpesvirus-68 (MHV68) reactivation in vivo, suggesting that coinfection with chronic pathogens is one mechanism herpesviruses can use to reactivate. To examine cell-specific MHV68 reactivation, we utilized conditional knockout mice to remove IL-4 receptor signaling on B cells or macrophages. We found that IL-4 signaling in combination with interferon-γ blockade reactivates MHV68 from latently infected macrophages, but not B cells. We continued our work on cell-specific reactivation signals by examining MHV68 infection in tissue resident peritoneal macrophages, called large peritoneal macrophages (LPMs), during coinfection with a parasite, Heligmosomoides polygyrus (HP). We found that coinfection with HP increases the number of MHV68-infected LPMs during acute replication and latency. Further, coinfected mice had increased ex vivo reactivation of MHV68. By using dietary and genetic depletion of the LPMs, we found that HP-induced expansion of the LPMs was necessary for the increased infection and reactivation. Overall, this work demonstrates a new role for LPMs during viral infection and highlights cell-specific mechanisms gammaherpesviruses use to reactivate from latency.

Author dc:creator

• Zarek, Christina Marie

Contributors dc:contributor

• Yan, Nan
• Hooper, Lora V.
• Pfeiffer, Julie K.
• Reese, Tiffany A.

• Coinfection
• Gammaherpesvirinae
• Herpesviridae Infections
• Latent Infection
• Macrophage Activation
• Parasitic Diseases

Language dc:language

en

Identifier

1482732372

OAI identifier oai:identifier

oai:utswmed-ir.tdl.org:2152.5/10453