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Virus genes and host correlates of pathology are markedly reduced during respiratory syncytial and influenza virus co-infection in BALB/c mice

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  • Virus genes and host correlates of pathology are markedly reduced during respiratory syncytial and influenza virus co-infection in BALB/c mice

    Heliyon. 2019 Jan 3;5(1):e01094. doi: 10.1016/j.heliyon.2018.e01094. eCollection 2019 Jan.
    Virus genes and host correlates of pathology are markedly reduced during respiratory syncytial and influenza virus co-infection in BALB/c mice.

    Ayegbusi OT1, Ajagbe OA1, Afowowe TO1, Aransi AT1, Olusola BA1, Awogbindin IO2, Ogunsemowo OO1, Faneye AO1, Odaibo GN1, Olaleye DO1.
    Author information

    Abstract

    Globally, influenza A virus (IAV) and respiratory syncytial virus (RSV) infection remain very high. There is also a high burden of IAV and RSV co-infection in developing countries. To develop universally protective vaccines against these infections, it is imperative that viral genes and immune correlates of pathology are elucidated. As such, we profiled virus genes expressions, histopathology and immunological responses of BALB/c mice infected with RSV and/or IAV in this study. RSV A2 and/or influenza A/H3N2/Perth/16/09 (Pr/H3N2) were induced over a seven-day period in BALB/c mice. Anaesthetized BALB/c mice (12-14 g) were divided into six groups (15-20 mice per group), inoculated with 32 μl each of 3LD50 Pr/H3N2 and/or 100 TCID50 RSV. Two groups (R or I) received RSV or Pr/H3N2 intranasally. Prior infection with either RSV or Pr/H3N2 was followed with a second challenge of the other virus 24 hours post inoculation in RI and IR groups. Another set was exposed to the two viruses simultaneously (I + R group) while the last group served as healthy controls. Five to seven mice per group were euthanized at days 2, 4 and 7. Lung and spleen organs were harvested for virus genes quantitation and immune cells phenotyping respectively. I + R group showed progressive downregulation of RSV F, G, NS1 and NS2 genes. IAV PB2 and M genes had high fold increase on day 2 and 4 post infections. However, by day 7 post infection, M and PB2 fold increase was lower. Also, increased proportions of NKT and T cell subsets were observed throughout the period in I + R group. Conversely, I group was characterized by reduced NKT cell counts and enhanced CD8 T cells levels while R group only showed an increased proportion of CD8 T cells towards the peak of infection. This study shows that RSV and IAV co-infection lead to reduced virulence and pathology compared to single infections. This information is very useful in combinatorial RSV/IAV vaccine design and development.


    KEYWORDS:

    Immunology; Virology

    PMID: 30623128 PMCID: PMC6319304 DOI: 10.1016/j.heliyon.2018.e01094
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