Early Virus-Host Interactions Dictate the Course of a Persistent Infection

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Lymphocytic Choriomenengitis Virus (LCMV) is an important model for the investigation of the pathogenesis of persistent viral infections. As with humans infected with hepatitis C and Human Immunodeficiency Virus-1, adult mice persistently infected with immunosuppressive strains of LCMV express high levels of negative immune regulators that suppress the adaptive T cell immune response thereby facilitating viral persistence. Unknown, however, is whether and how very early interactions between the virus and the infected host affect the establishment of a persistent infection. Here, we describe host-virus interactions within the first 8–12 hours of infection are critical for establishing a persistent infection. While early induction of an anti-viral type-I interferons is essential for the subsequent adaptive immune response required to clear the virus, LCMV is able to overcome the programmed innate immune response by over-stimulating this response early. This affects not only the rate of viral growth in the host, but also the ability to infect specific immune cells that help shape an effective adaptive immune response. We further describe how and where LCMV is sensed by this early immune response, identify the critical timing of early virus-host interactions that lead to a persistent infection, and identify an early dysregulated immune signature associated with a persistent viral infection. Altogether, these observations are critical to understanding how early virus-host interactions determines the course of infection.

Vyšlo v časopise: Early Virus-Host Interactions Dictate the Course of a Persistent Infection. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004588
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004588

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