Latent gammaherpesvirus infection enhances type I IFN response and reduces virus spread in an influenza A virus co-infection model: Latent gammaherpesvirus infection leads to a more rapid type I interferon response which protects mice against a severe influenza A virus infection

Gareth Hardisty, Marylynne Q Nicol, Darren Shaw, Ian D Bennett, Karen Bryson, Yvonne Ligertwood, Jürgen Schwarze, Pip Beard, John Hopkins, Bernadette Dutia

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Infections with persistent or latent viruses alter host immune homeostasis and have potential to affect the outcome of concomitant acute viral infections such as influenza A virus (IAV). Gammaherpesviruses establish life-long infections and
require an on-going immune response to control reactivation. We have used a murine model of co-infection to investigate the response to IAV infection in mice latently infected with the gammaherpesvirus MHV-68. Over the course of infection, latently infected BALB/c mice showed less weight loss, clinical signs, pulmonary cellular infiltration and expression of inflammatory mediators than naïve mice infected with IAV and had significantly more activated CD8+
T cells in the lungs.
Four days after IAV infection, virus spread in the lungs of latently infected animals was significantly lower than in naïve animals. By 7 days after IAV infection latently infected lungs express elevated levels of cytokines and chemokines indicating they are primed to respond to the secondary infection. Investigation at an early time point showed that 24 h after IAV infection co-infected animals had higher expression of IFNβ and Ddx58 (RIG-I) and a range of ISGs than mice infected with
IAV alone suggesting that the type I IFN response plays a role in the protective effect. This effect was mouse strain dependent and did not occur in 129/Sv/Ev mice. These results offer insight into innate immune mechanisms that could be utilized to protect against IAV infection and highlight on-going and persistent viral infections as a significant factor impacting the severity of acute respiratory infections.
Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalJournal of General Virology
Volume105
Issue number2
Early online date8 Feb 2024
DOIs
Publication statusPublished - 2024

Keywords / Materials (for Non-textual outputs)

  • Co-infections
  • innate immune response
  • heterologous protection
  • ISGs

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  • ISP 2017/22-Dutia Bernadette

    Dutia, B.

    BBSRC

    1/04/1731/03/22

    Project: Research

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