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HIV-1 clade promoters strongly influence spatial and temporal dynamics of viral replication in vivo
- Source :
- Journal of Clinical Investigation, Journal of Clinical Investigation, 2010, 115 (2), pp.348-58. ⟨10.1172/JCI200522873⟩, Journal of Clinical Investigation, American Society for Clinical Investigation, 2010, 115 (2), pp.348-58. ⟨10.1172/JCI200522873⟩, Journal of clinical investigation, 115(2), 348-358. The American Society for Clinical Investigation
- Publication Year :
- 2010
- Publisher :
- HAL CCSD, 2010.
-
Abstract
- International audience; Although the primary determinant of cell tropism is the interaction of viral envelope or capsid proteins with cellular receptors, other viral elements can strongly modulate viral replication. While the HIV-1 promoter is polymorphic for a variety of transcription factor binding sites, the impact of these polymorphisms on viral replication in vivo is not known. To address this issue, we engineered isogenic SIVmac239 chimeras harboring the core promoter/enhancer from HIV-1 clades B, C, and E. Here it is shown that the clade C and E core promoters/enhancers bear a noncanonical activator protein-1 (AP-1) binding site, absent from the corresponding clade B region. Relative ex vivo replication of chimeras was strongly dependent on the tissue culture system used. Notably, in thymic histocultures, replication of the clade C chimera was favored by IL-7 enrichment, which suggests that the clade C polymorphism in the AP-1 and NF-kappaB binding sites is involved. Simultaneous infection of rhesus macaques with the 3 chimeras revealed a strong predominance of the clade C chimera during primary infection. Thereafter, the B chimera dominated in all tissues. These data show that the clade C promoter is particularly adapted to sustain viral replication in primary viremia and that clade-specific promoter polymorphisms constitute a major determinant for viral replication.
- Subjects :
- Simian Acquired Immunodeficiency Syndrome
MESH: NF-kappa B
HIV Infections
Virus Replication
Tissue Culture Techniques
MESH: HIV-1
MESH: Capsid
MESH: Animals
Promoter Regions, Genetic
MESH: Organ Specificity
MESH: Receptors, Cell Surface
0303 health sciences
MESH: Infant, Newborn
NF-kappa B
General Medicine
MESH: HIV Infections
MESH: Transcription Factor AP-1
3. Good health
MESH: Promoter Regions (Genetics)
Organ Specificity
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Simian Immunodeficiency Virus
MESH: Simian Acquired Immunodeficiency Syndrome
MESH: Simian immunodeficiency virus
Receptors, Cell Surface
Thymus Gland
Article
MESH: Macaca mulatta
03 medical and health sciences
Capsid
Organ Culture Techniques
Species Specificity
MESH: Polymorphism, Genetic
Animals
Humans
MESH: Species Specificity
MESH: Tissue Culture Techniques
030304 developmental biology
Polymorphism, Genetic
MESH: Humans
030306 microbiology
Interleukin-7
MESH: Virus Replication
Infant, Newborn
MESH: Thymus Gland
Macaca mulatta
MESH: Interleukin-7
MESH: Organ Culture Techniques
Transcription Factor AP-1
HIV-1
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Investigation, Journal of Clinical Investigation, 2010, 115 (2), pp.348-58. ⟨10.1172/JCI200522873⟩, Journal of Clinical Investigation, American Society for Clinical Investigation, 2010, 115 (2), pp.348-58. ⟨10.1172/JCI200522873⟩, Journal of clinical investigation, 115(2), 348-358. The American Society for Clinical Investigation
- Accession number :
- edsair.doi.dedup.....5975dc4567a87ce797975c68e317e505