UNASSIGNED: Airway epithelial cells are susceptible to @entity281 viruses (IAV), resulting in productive virus replication and release. Macrophages (M  ) are also permissive to IAV @entity778 replication is abortive. Currently, it is unclear how productive @entity281 of M   is impaired or the extent to which seasonal IAV replicate in M  . Herein, we compared @entity19 M   and epithelial cells for their ability to support genomic replication and transcription, synthesis of viral proteins, assembly of virions and release of infectious progeny following exposure to genetically defined IAV. We confirm that seasonal IAV differ in their ability to utilize cell-surface receptors for infectious entry and that this represents one level of virus restriction. Following virus entry, we demonstrate synthesis of all 8 segments of genomic viral (v)RNA and messenger (m)RNA, as well as 7 distinct IAV proteins, in IAV-infected @entity19 M  . Although newly synthesized hemagglutinin (HA) and neuraminidase (NA) glycoproteins are incorporated into the plasma membrane and expressed at the cell surface, electron microscopy confirmed that virus assembly was defective in IAV-infected M  , defining a second level of restriction late in the virus life cycle. IMPORTANCE: Seasonal influenza A viruses (IAV) and highly pathogenic avian influenza (HPAI) infect macrophages, but only HPAI replicate productively in these cells. Herein, we demonstrate that impaired virus uptake into macrophages represents one level of restriction limiting @entity281 by seasonal IAV. Following uptake, seasonal IAV do not complete productive replication in macrophages, representing a second level of restriction. Using @entity19 macrophages, we demonstrate that productive @entity281 is blocked late in the virus life cycle, such that virus assembly is defective and newly synthesized virions are not released. These studies represent an important step towards identifying host-encoded factors that block replication of seasonal IAV, but not HPAI, in macrophages.

Infection of XXXX macrophages by seasonal influenza viruses can be restricted at the level of virus entry and at late stage in the virus life cycle.

@entity778 :: ('MESH:D015658', 'Disease') :: ['infection, however virus'] @entity281 :: ('MESH:D007239', 'Disease') :: ['infection with seasonal influenza A', 'infection'] @entity19 :: ('10090', 'Species') :: ['mouse', 'murine']
@entity19 :: (10090,Species) :: ['mouse']
