Loss of Resistance to Mousepox during Chronic Lymphocytic Choriomeningitis Virus Infection Is Associated with Impaired T-Cell Responses and Can Be Rescued by Immunization

Author:

Alves-Peixoto Pedro123ORCID,Férez Maria1,Knudson Cory J.1,Melo-Silva Carolina R.1,Stotesbury Colby1,Wong Eric B.1,Correia-Neves Margarida23,Sigal Luis J.1ORCID

Affiliation:

1. Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

2. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

3. ICVS/3B’s—PT Government Associate Laboratory, Braga/Guimarães, Portugal

Abstract

Chronic viral infections may result in immunosuppression and enhanced susceptibility to infections with other pathogens. For example, we have recently shown that mice chronically infected with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13) are highly susceptible to mousepox, a disease that is caused by ectromelia virus and that is the mouse homolog of human smallpox. Here we show chronic CL13 infection severely disrupts the expansion, proliferation, activation, and cytotoxicity of T cells in response due at least in part to the suppressive effects of the chronic infection milieu. Notably, despite this profound immunodeficiency, mice chronically infected with CL13 could be protected by vaccination with a highly attenuated variant of ECTV. These results demonstrate that protective vaccination of immunosuppressed individuals is possible, provided that proper immunization tools are used.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

MEC | Fundação para a Ciência e a Tecnologia

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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