title: Covert human immunodeficiency virus replication in dendritic cells and in DC-SIGN-expressing cells promotes long-term transmission to lymphocytes.
abstract: HIV-1 virions are efficiently captured by monocyte-derived immature dendritic cells (iDCs), as well as by cell lines expressing the lectin DC-SIGN. Viral infectivity can be retained for several days, and even enhanced, before transmission to CD4+ lymphocytes. The role of DC-SIGN in viral retention and enhancement of infection is not fully understood and varies according to the cell line expressing the lectin. We studied here the mechanisms underlying this process. We focused our study on X4-tropic human immunodeficiency virus (HIV) strains, since they were widely believed not to replicate in iDCs. However, we first show that X4 HIV replicates covertly and slowly in iDCs. This is also the case in Raji-DC-SIGN cells, which are classically used to study HIV transmission. We used either single-cycle or replicative HIV and measured viral RT and replication to further demonstrate that transfer of incoming virions from iDCs or DC-SIGN+ cells occurs only on the short-term (i.e., a few hours after viral exposure). There is no long-term storage of original HIV particles in these cells. A few days after viral exposure, replicative viruses, and not single-cycle virions, are transmitted to CD4+ cells. The cell-type-dependent activity of DC-SIGN reflects the ability of HIV to replicate covertly in some cells, and not in others.
authors.affiliation: Institut Pasteur, Groupe Virus et Immunité, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France. schwartz@pasteur.fr
authors.forename: Cinzia
authors.initials: C
authors.lastname: Nobile
authors.forename: Caroline
authors.initials: C
authors.lastname: Petit
authors.forename: Arnaud
authors.initials: A
authors.lastname: Moris
authors.forename: Katharina
authors.initials: K
authors.lastname: Skrabal
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Abastado
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mammano
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000378:metabolism*; D048348:Reverse Transcription; D013997:Time Factors; D014779:Virus Replication; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin