title: Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques.
abstract: BACKGROUND
  Extensive studies of primary infection are crucial to our understanding of the course of HIV disease. In SIV-infected macaques, a model closely mimicking HIV pathogenesis, we used a combination of three markers -- viral RNA, 2LTR circles and viral DNA -- to evaluate viral replication and dissemination simultaneously in blood, secondary lymphoid tissues, and the gut during primary and chronic infections. Subsequent viral compartmentalization in the main target cells of the virus in peripheral blood during the chronic phase of infection was evaluated by cell sorting and viral quantification with the three markers studied.
  
  
  RESULTS
  The evolutions of viral RNA, 2LTR circles and DNA levels were correlated in a given tissue during primary and early chronic infection. The decrease in plasma viral load principally reflects a large decrease in viral replication in gut-associated lymphoid tissue (GALT), with viral RNA and DNA levels remaining stable in the spleen and peripheral lymph nodes. Later, during chronic infection, a progressive depletion of central memory CD4+ T cells from the peripheral blood was observed, accompanied by high levels of viral replication in the cells of this subtype. The virus was also found to replicate at this point in the infection in naive CD4+ T cells. Viral RNA was frequently detected in monocytes, but no SIV replication appeared to occur in these cells, as no viral DNA or 2LTR circles were detected.
  
  
  CONCLUSIONS
  We demonstrated the persistence of viral replication and dissemination, mostly in secondary lymphoid tissues, during primary and early chronic infection. During chronic infection, the central memory CD4+ T cells were the major site of viral replication in peripheral blood, but viral replication also occurred in naive CD4+ T cells. The role of monocytes seemed to be limited to carrying the virus as a cargo because there was an observed lack of replication in these cells. These data may have important implications for the targeting of HIV treatment to these diverse compartments.
authors.affiliation: CEA, Division of Immuno-Virology, DSV/iMETI, Fontenay-aux-Roses, France. abdelkrim.mannioui@cea.fr
authors.forename: Abdelkrim
authors.initials: A
authors.lastname: Mannioui
authors.forename: Olivier
authors.initials: O
authors.lastname: Bourry
authors.forename: Pierre
authors.initials: P
authors.lastname: Sellier
authors.forename: Benoit
authors.initials: B
authors.lastname: Delache
authors.forename: Patricia
authors.initials: P
authors.lastname: Brochard
authors.forename: Thibault
authors.initials: T
authors.lastname: Andrieu
authors.forename: Bruno
authors.initials: B
authors.lastname: Vaslin
authors.forename: Ingrid
authors.initials: I
authors.lastname: Karlsson
authors.forename: Pierre
authors.initials: P
authors.lastname: Roques
authors.forename: Roger
authors.initials: R
authors.lastname: Le Grand
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018450:Disease Progression; D007156:Immunologic Memory; D008221:Lymphoid Tissue / Q000276:immunology / Q000821:virology*; D008252:Macaca fascicularis; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
chemical_list: D012367:RNA, Viral