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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. DESIGN: 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.
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https://hal-riip.archives-ouvertes.fr/pasteur-00850258
Contributor : Peter Sommer <>
Submitted on : Tuesday, August 6, 2013 - 4:34:45 AM
Last modification on : Monday, January 13, 2020 - 5:08:10 PM

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Mireille Centlivre, Peter Sommer, Marie Michel, Raphaël Ho Tsong Fang, Sandrine Gofflo, et al.. The HIV-1 clade C promoter is particularly well adapted to replication in the gut in primary infection.. AIDS, Lippincott, Williams & Wilkins, 2006, 20 (5), pp.657-66. ⟨10.1097/01.aids.0000216365.38572.2f⟩. ⟨pasteur-00850258⟩

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