Influenza Virus Overcomes Cellular Blocks To Productively Replicate, Impacting Macrophage Function.

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Macrophages are crucial for innate immunity against respiratory pathogens like influenza.
• The capacity of influenza viruses to productively replicate in macrophages has been debated.
• Previous studies indicated limited replication of highly pathogenic avian influenza H5N1 strains in macrophages.

Purpose of the Study:

• To investigate the extent of productive influenza virus replication in macrophages.
• To identify cellular blocks limiting influenza virus replication in macrophages.
• To determine the impact of productive viral replication on macrophage functions.

Main Methods:

• Tested replication of 28 human, avian, and swine influenza viruses in murine and primary human macrophages.
• Assessed viral entry, replication blocks, cytotoxicity, nitric oxide, reactive oxygen species, and phagocytosis.
• Quantified Fc receptor (CD16, CD32) surface levels on macrophages.

Main Results:

• Only a subset of influenza viruses productively replicated in macrophages, overcoming cellular blocks.
• Murine macrophages exhibited blocks during viral entry (HA-mediated) and post-entry.
• Human macrophages had a single post-late protein synthesis block.
• Productive replication reduced phagocytosis of IgG-opsonized bioparticles and decreased Fc receptor surface levels.

Conclusions:

• Influenza virus replication in macrophages is possible for specific strains by overcoming cellular blocks.
• Productive replication impairs macrophage phagocytic function, a novel finding for RNA viruses.
• These findings reveal new insights into influenza virus pathogenicity and host-pathogen interactions.