Preexisting helminth challenge exacerbates infection and reactivation of gammaherpesvirus in tissue resident macrophages.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, c2005-

Coinfection* ; Herpesviridae Infections*/complications ; Gammaherpesvirinae*/physiology ; Latent Infection* ; Helminths* ; Parasitic Diseases*; Humans ; Animals ; Mice ; Virus Activation ; Virus Latency/physiology ; Vitamin A ; B-Lymphocytes ; Macrophages ; Mice, Inbred C57BL

Competing Interests: The authors have declared that no competing interests exist.
Even though gammaherpesvirus and parasitic infections are endemic in parts of the world, there is a lack of understanding about the outcome of coinfection. In humans, coinfections usually occur sequentially, with fluctuating order and timing in different hosts. However, experimental studies in mice generally do not address the variables of order and timing of coinfections. We sought to examine the variable of coinfection order in a system of gammaherpesvirus-helminth coinfection. Our previous work demonstrated that infection with the intestinal parasite, Heligmosomoides polygyrus, induced transient reactivation from latency of murine gammaherpesvirus-68 (MHV68). In this report, we reverse the order of coinfection, infecting with H. polygyrus first, followed by MHV68, and examined the effects of preexisting parasite infection on MHV68 acute and latent infection. We found that preexisting parasite infection increased the propensity of MHV68 to reactivate from latency. However, when we examined the mechanism for reactivation, we found that preexisting parasite infection increased the ability of MHV68 to reactivate in a vitamin A dependent manner, a distinct mechanism to what we found previously with parasite-induced reactivation after latency establishment. We determined that H. polygyrus infection increased both acute and latent MHV68 infection in a population of tissue resident macrophages, called large peritoneal macrophages. We demonstrate that this population of macrophages and vitamin A are required for increased acute and latent infection during parasite coinfection.
(Copyright: © 2023 Zarek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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R01 AI130020 United States AI NIAID NIH HHS; R01 DK070855 United States DK NIDDK NIH HHS; T32 AI005284 United States AI NIAID NIH HHS; U19 AI142784 United States AI NIAID NIH HHS

11103-57-4 (Vitamin A)

Date Created: 20231017 Date Completed: 20231023 Latest Revision: 20240210

20250114

PMC10581490

10.1371/journal.ppat.1011691

37847677