title: Dendritic cell-mediated HIV-1 infection of T cells demonstrates a direct relationship to plasma viral RNA levels.
abstract: OBJECTIVE
  To examine the relationship between infectivity of HIV-1 variants in dendritic cell (DC)-mediated in trans infection of T cells and plasma viral RNA levels in infected subjects.
  
  
  METHODS
  HIV-1 was isolated from peripheral blood mononuclear cells of chronically infected individuals, typed for coreceptor usage, and viral replication were examined in monocyte-derived DCs-peripheral blood lymphocytes cocultures. The rate of p24 antigen production during the logarithmic phase of viral replication was determined by enzyme-linked immunosorbent assay. Additionally, nef variants were cloned and expressed in trans with a HIV luciferase vector and CCR5-tropic HIV-1 envelope, and infectivity was measured in DC-mediated capture-transfer assays.
  
  
  RESULTS
  Replication capacity of HIV-1 viral CCR5-tropic isolates in monocyte-derived dendritic cells-peripheral blood lymphocytes cocultures was linearly associated with the plasma viral RNA levels in a cohort of HIV-1-infected individuals exhibiting an inverse relationship between plasma viral RNA and CD4 cell count. Furthermore, infectivity activity of nef variants in context of DC-mediated enhanced infection of T cells also showed a linear relationship to plasma viral RNA levels.
  
  
  CONCLUSIONS
  These results illustrate that replication capacity of HIV-1 in DC T-cell cultures is a significant determinant of plasma viral RNA level. The data suggest that adaptation of HIV-1 to DC interactions with T cells influences the level of viral replication in the host.
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Reetakshi
authors.initials: R
authors.lastname: Arora
authors.forename: Lara
authors.initials: L
authors.lastname: Bull
authors.forename: Edward B
authors.initials: EB
authors.lastname: Siwak
authors.forename: Rajesh
authors.initials: R
authors.lastname: Thippeshappa
authors.forename: Roberto C
authors.initials: RC
authors.lastname: Arduino
authors.forename: Jason T
authors.initials: JT
authors.lastname: Kimata
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D003713:Dendritic Cells / Q000821:virology*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood*; D019713:Receptors, CCR5 / Q000235:genetics; D013601:T-Lymphocytes / Q000821:virology*; D019562:Viral Load; D014779:Virus Replication / Q000502:physiology
chemical_list: D012367:RNA, Viral; D019713:Receptors, CCR5
references.citation: Virology. 2008 Jan 5;370(1):184-93
references.pmid: 17904609
references.citation: Science. 2003 May 23;300(5623):1295-7
references.pmid: 12730499
references.citation: Genes Immun. 2007 Apr;8(3):224-31
references.pmid: 17330138
references.citation: J Virol. 2002 Dec;76(23):11827-36
references.pmid: 12414925
references.citation: J Virol. 2002 Nov;76(21):10692-701
references.pmid: 12368311
references.citation: J Exp Med. 2004 Sep 20;200(6):749-59
references.pmid: 15365096
references.citation: AIDS Res Hum Retroviruses. 2002 May 20;18(8):567-76
references.pmid: 12036486
references.citation: Science. 1993 Mar 19;259(5102):1749-54
references.pmid: 8096089
references.citation: Curr HIV Res. 2006 Jan;4(1):65-77
references.pmid: 16454712
references.citation: J Virol. 2002 Jul;76(13):6425-34
references.pmid: 12050354
references.citation: Nat Rev Immunol. 2006 Nov;6(11):859-68
references.pmid: 17063186
references.citation: Nat Rev Immunol. 2008 Jun;8(6):447-57
references.pmid: 18469831
references.citation: Ann Intern Med. 2001 May 15;134(10):978-96
references.pmid: 11352699
references.citation: Nature. 1993 Mar 25;362(6418):355-8
references.pmid: 8455722
references.citation: J Virol. 1999 Feb;73(2):1655-60
references.pmid: 9882375
references.citation: Nat Med. 1996 Nov;2(11):1240-3
references.pmid: 8898752
references.citation: Nat Rev Immunol. 2005 Oct;5(10):783-92
references.pmid: 16200081
references.citation: Curr Opin Infect Dis. 2003 Feb;16(1):11-8
references.pmid: 12821824
references.citation: Virology. 2004 Oct 1;327(2):307-17
references.pmid: 15351218
references.citation: Virology. 2006 Aug 1;351(2):322-39
references.pmid: 16684552
references.citation: Science. 2005 Mar 4;307(5714):1434-40
references.pmid: 15637236
references.citation: J Exp Med. 1996 Feb 1;183(2):687-92
references.pmid: 8627183
references.citation: AIDS Res Hum Retroviruses. 1996 Mar 1;12(4):337-45
references.pmid: 8906995
references.citation: J Virol. 2009 Jan;83(2):1093-104
references.pmid: 18987145
references.citation: N Engl J Med. 1996 Feb 15;334(7):426-31
references.pmid: 8552144
references.citation: J Virol. 1993 Aug;67(8):4639-50
references.pmid: 8043040
references.citation: J Exp Med. 2004 Nov 15;200(10):1279-88
references.pmid: 15545354
references.citation: Infection. 2005 Jun;33(3):160-2
references.pmid: 15940420
references.citation: Cell. 1996 Aug 9;86(3):367-77
references.pmid: 8756719
references.citation: Science. 1996 May 24;272(5265):1167-70
references.pmid: 8638160
references.citation: Ann Intern Med. 1995 Apr 15;122(8):573-9
references.pmid: 7887550
references.citation: Cell. 1994 Aug 12;78(3):389-98
references.pmid: 7914836
references.citation: Ann Intern Med. 2001 May 1;134(9 Pt 1):761-76
references.pmid: 11329234
references.citation: Nat Med. 1999 May;5(5):535-41
references.pmid: 10229230
references.citation: Nat Med. 1999 Jul;5(7):723-5
references.pmid: 10395309
references.citation: J Clin Microbiol. 1992 Jul;30(7):1787-94
references.pmid: 1629336
references.citation: J Virol. 1996 Nov;70(11):7752-64
references.pmid: 8892896
references.citation: J Virol. 2001 May;75(10):4664-72
references.pmid: 11312337
references.citation: J Infect Dis. 1998 Mar;177(3):600-10
references.pmid: 9498438
references.citation: J Virol. 2007 Mar;81(5):2497-507
references.pmid: 17151103
references.citation: J Virol. 2007 Feb;81(3):1534-6
references.pmid: 17108041
references.citation: Science. 1992 Jul 17;257(5068):383-7
references.pmid: 1352913