title: Effect of HIV-1 Env on SERINC5 Antagonism.
abstract: SERINC5 is able to restrict HIV-1 infection by drastically impairing the infectivity of viral particles. Studies have shown that the HIV-1 Nef protein counters SERINC5 through downregulating SERINC5 from the cell surface and preventing the virion incorporation of SERINC5. In addition, the Env proteins of some HIV-1 strains can also overcome SERINC5 inhibition. However, it is unclear how HIV-1 Env does so and why HIV-1 has two mechanisms to resist SERINC5 inhibition. The results of this study show that neither Env nor Nef prevents high levels of ectopic SERINC5 from being incorporated into HIV-1 particles, except that Env, but not Nef, is able to resist inhibition by virion-associated SERINC5. Testing of a panel of HIV-1 Env proteins from different subtypes revealed a high frequency of SERINC5-resistant Envs. Interestingly, although the SERINC5-bearing viruses were not inhibited by SERINC5 itself, they became more sensitive to the CCR5 inhibitor maraviroc and some neutralizing antibodies than the SERINC5-free viruses, which suggests a possible influence of SERINC5 on Env function. We conclude that HIV-1 Env is able to overcome SERINC5 without preventing SERINC5 virion incorporation.
  
  
  
  HIV-1 Nef is known to enhance the infectivity of HIV-1 particles and to contribute to the maintenance of high viral loads in patients. However, the underlying molecular mechanism remained elusive until the recent discovery of the antiviral activity of SERINC5. SERINC5 profoundly inhibits HIV-1 but is antagonized by Nef, which prevents the incorporation of SERINC5 into viral particles. Here, we show that HIV-1 Env, but not Nef, is able to resist high levels of SERINC5 without excluding SERINC5 from incorporation into viral particles. However, the virion-associated SERINC5 renders HIV-1 more sensitive to some broadly neutralizing antibodies. It is possible that, under the pressure of some neutralizing antibodies in vivo, HIV-1 needs Nef to remove SERINC5 from viral particles, even though viral Env is able to resist virion-associated SERINC5.
authors.affiliation: Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.|Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
authors.forename: Saina
authors.initials: S
authors.lastname: Beitari
authors.affiliation: Centre de Recherche du CHUM Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Shilei
authors.initials: S
authors.lastname: Ding
authors.affiliation: Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.|Centre de Recherche du CHUM Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Andrés
authors.initials: A
authors.lastname: Finzi
authors.affiliation: Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada chen.liang@mcgill.ca.|Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.|Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
mesh_terms: D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D020128:Inhibitory Concentration 50; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; C028391:G protein, vesicular stomatitis virus; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010446:Peptide Fragments; C000602387:SERINC5 protein, human; D014759:Viral Envelope Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1
keywords: Env; Nef; SERINC5; human immunodeficiency virus