Lst1 deficiency has a minor impact on course and outcome of the host response to influenza A H1N1 infections in mice

Virol J. 2016 Jan 27:13:17. doi: 10.1186/s12985-016-0471-0.

Abstract

Background: Previously, we performed a quantitative trait locus (QTL) mapping study in BXD recombinant inbred mice to identify host genetic factors that confer resistance to influenza A virus infection. We found Lst1 (leukocyte specific transcript 1) as one of the most promising candidate genes in the Qivr17-2 locus because it is non-functional in DBA/2 J mice. Several studies have proposed that LST1 plays a role in the immune response to inflammatory diseases in humans and has additional immune-regulatory functions. Here, we evaluated the relevance of LST1 for the host response to influenza A infection in B6-Lst1 (-/-) mutant mice.

Findings: To investigate the role of LST1, we infected B6-Lst1 (-/-) mutant and C57BL/6 N wild-type mice with a low-virulent influenza A virus (PR8M; H1N1). Lst1 deficient mice exhibited significantly increased body weight loss at days 5 and 6 after infection and slightly increased lethality compared to infected wild-type mice. Determination of viral loads, histopathological examination and analysis of immune cell composition in bronchoalveolar lavage of infected lungs did not reveal any obvious differences between KO and wild-type mice.

Conclusions: The absence of Lst1 leads to a slightly more susceptible phenotype. However, deletion of Lst1 in DBA/2 J mice alone does not explain the high susceptibility of this strain to PR8M influenza infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Disease Susceptibility
  • Female
  • Host-Pathogen Interactions*
  • Influenza A Virus, H1N1 Subtype / physiology*
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / deficiency*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Knockout
  • Orthomyxoviridae Infections / genetics*
  • Orthomyxoviridae Infections / mortality
  • Orthomyxoviridae Infections / virology*
  • Phenotype
  • Viral Load

Substances

  • Intracellular Signaling Peptides and Proteins
  • LST1 protein, human
  • Membrane Proteins