title: HIV-1 and its gp120 inhibits the influenza A(H1N1)pdm09 life cycle in an IFITM3-dependent fashion.
abstract: HIV-1-infected patients co-infected with A(H1N1)pdm09 surprisingly presented benign clinical outcome. The knowledge that HIV-1 changes the host homeostatic equilibrium, which may favor the patient resistance to some co-pathogens, prompted us to investigate whether HIV-1 infection could influence A(H1N1)pdm09 life cycle in vitro. We show here that exposure of A(H1N1)pdm09-infected epithelial cells to HIV-1 viral particles or its gp120 enhanced by 25% the IFITM3 content, resulting in a decrease in influenza replication. This event was dependent on toll-like receptor 2 and 4. Moreover, knockdown of IFITM3 prevented HIV-1 ability to inhibit A(H1N1)pdm09 replication. HIV-1 infection also increased IFITM3 levels in human primary macrophages by almost 100%. Consequently, the arrival of influenza ribonucleoproteins (RNPs) to nucleus of macrophages was inhibited, as evaluated by different approaches. Reduction of influenza RNPs entry into the nucleus tolled A(H1N1)pdm09 life cycle in macrophages earlier than usual, limiting influenza's ability to induce TNF-α. As judged by analysis of the influenza hemagglutin (HA) gene from in vitro experiments and from samples of HIV-1/A(H1N1)pdm09 co-infected individuals, the HIV-1-induced reduction of influenza replication resulted in delayed viral evolution. Our results may provide insights on the mechanisms that may have attenuated the clinical course of Influenza in HIV-1/A(H1N1)pdm09 co-infected patients during the recent influenza form 2009/2010.
authors: Respiratory Viruses Laboratory, WHO/NIC, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, RJ, Brazil.
authors: Milene
authors: M
authors: Mesquita
authors: Respiratory Viruses Laboratory, WHO/NIC, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, RJ, Brazil.
authors: Natalia
authors: N
authors: Fintelman-Rodrigues
authors: Respiratory Viruses Laboratory, WHO/NIC, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, RJ, Brazil.
authors: Carolina Q
authors: CQ
authors: Sacramento
authors: Respiratory Viruses Laboratory, WHO/NIC, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, RJ, Brazil.
authors: Juliana L
authors: JL
authors: Abrantes
authors: Respiratory Viruses Laboratory, WHO/NIC, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, RJ, Brazil.
authors: Eduardo
authors: E
authors: Costa
authors: Laboratory on Thymus Research, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, RJ, Brazil.
authors: Jairo R
authors: JR
authors: Temerozo
authors: Respiratory Viruses Laboratory, WHO/NIC, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, RJ, Brazil.
authors: Marilda M
authors: MM
authors: Siqueira
authors: Laboratory on Thymus Research, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, RJ, Brazil.
authors: Dumith Chequer
authors: DC
authors: Bou-Habib
authors: Respiratory Viruses Laboratory, WHO/NIC, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, RJ, Brazil.
authors: Thiago Moreno L
authors: TM
authors: Souza
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D004285:Dogs; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology / Q000821:virology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000502:physiology*; D007372:Interferons / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D008565:Membrane Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; C080082:IFITM3 protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D007372:Interferons