title: The HIV-1 clade C promoter is particularly well adapted to replication in the gut in primary infection.
abstract: OBJECTIVE
  Coinfection of rhesus macaques with human/simian immunodeficiency virus chimeras harbouring the minimal core-promoter/enhancer elements from HIV-1 clade B, C and E viral prototypes (STR-B, STR-C and STR-E) revealed a remarkable dichotomy in terms of spatio-temporal viral replication. The clade C chimera (STR-C) predominated in primary infection. The present study was aimed at identifying the origin of STR-C plasma viraemia at this infection phase.
  
  
  METHODS
  By competing isogenic viruses differing only in their promoters, it was possible to identify subtle phenotypical differences in viral replication kinetics and compartmentalization in vivo.
  
  
  METHODS
  Two rhesus macaques were coinfected by the three STR chimeras and the relative colonization of different compartments, particularly blood and stool, was determined for each chimera. Moreover, growth competition experiments in thymic histocultures enriched in interleukin (IL)-7 were performed and relative percentages of chimeras were estimated in supernatants and thymocytes lysates at different time points.
  
  
  RESULTS
  It is demonstrated here that at the peak of primary infection, preferential replication of STR-C was supported by the gut-associated lymphoid tissue (GALT), an IL-7 rich microenvironment. This was shown by the correlation of the RNA viral genotype in blood and stools, compartments directly draining virions from the GALT. Thymic histocultures confirmed that replication of STR-C is particularly susceptible to this cytokine, compared to its STR-B and STR-E counterparts.
  
  
  CONCLUSIONS
  These data show that the GALT cytokine network may well favour HIV-1 clade C replication during primary infection. This could result in enhanced transmission.
authors.affiliation: Unité de Rétrovirologie Moléculaire, Institut Pasteur, Paris, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Centlivre
authors.forename: Peter
authors.initials: P
authors.lastname: Sommer
authors.forename: Marie
authors.initials: M
authors.lastname: Michel
authors.forename: Raphaël
authors.initials: R
authors.lastname: Ho Tsong Fang
authors.forename: Sandrine
authors.initials: S
authors.lastname: Gofflo
authors.forename: Jenny
authors.initials: J
authors.lastname: Valladeau
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schmitt
authors.forename: Simon
authors.initials: S
authors.lastname: Wain-Hobson
authors.forename: Monica
authors.initials: M
authors.lastname: Sala
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D002678:Chimera; D004279:DNA, Viral / Q000032:analysis; D005243:Feces / Q000821:virology; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D015851:Interleukin-7 / Q000276:immunology; D007422:Intestines / Q000276:immunology* / Q000821:virology; D008221:Lymphoid Tissue / Q000821:virology*; D008253:Macaca mulatta; D011401:Promoter Regions, Genetic; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology; D020079:Terminal Repeat Sequences; D014766:Viremia; D014779:Virus Replication / Q000235:genetics*
chemical_list: D004279:DNA, Viral; D015851:Interleukin-7; D012367:RNA, Viral