title: Nef-mediated enhancement of virion infectivity and stimulation of viral replication are fundamental properties of primate lentiviruses.
abstract: Nef is a multifunctional accessory protein of primate lentiviruses. Recently, it has been shown that the ability of Nef to downmodulate CD4, CD28, and class I major histocompatibility complex is highly conserved between most or all primate lentiviruses, whereas Nef-mediated downregulation of T-cell receptor-CD3 was lost in the lineage that gave rise to human immunodeficiency virus type 1 (HIV-1). Whether or not other Nef activities are preserved between different groups of primate lentiviruses remained to be determined. Here, we show that nef genes from a large variety of HIVs and simian immunodeficiency viruses (SIVs) enhance virion infectivity and stimulate viral replication in human cells and/or in ex vivo infected human lymphoid tissue (HLT). Notably, nef alleles from unpassaged SIVcpz and SIVsmm enhanced viral infectivity, replication, and cytopathicity in cell culture and in ex vivo infected HLT as efficiently as those from HIV-1 and HIV-2, their human counterparts. Furthermore, nef genes from several highly divergent SIVs that have not been found in humans were also highly active in human cells and/or tissues. Thus, most primate lentiviral Nefs enhance virion infectivity and stimulate viral replication. Moreover, our data show that SIVcpz and SIVsmm Nefs do not require adaptive changes to perform these functions in human cells or tissues and support the idea that nef alleles from other primate lentiviruses would also be capable of promoting efficient virus spread in humans.
authors.affiliation: Institute of Virology, University of Ulm, Albert Einstein Allee 11, D-89081 Ulm, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Münch
authors.forename: Devi
authors.initials: D
authors.lastname: Rajan
authors.forename: Michael
authors.initials: M
authors.lastname: Schindler
authors.forename: Anke
authors.initials: A
authors.lastname: Specht
authors.forename: Elke
authors.initials: E
authors.lastname: Rücker
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Novembre
authors.forename: Eric
authors.initials: E
authors.lastname: Nerrienet
authors.forename: Michaela C
authors.initials: MC
authors.lastname: Müller-Trutwin
authors.forename: Martine
authors.initials: M
authors.lastname: Peeters
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
mesh_terms: D000818:Animals; D002460:Cell Line; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D006367:HeLa Cells; D006801:Humans; D009924:Organ Culture Techniques; D014066:Palatine Tonsil / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D014771:Virion / Q000472:pathogenicity*; D014779:Virus Replication / Q000187:drug effects* / Q000941:ethics; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: C429284:NEF protein, SIV; D054334:Viral Regulatory and Accessory Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus