A decline in CCL3-5 chemokine gene expression during primary simian-human immunodeficiency virus infection.
BACKGROUND
The CC-chemokines CCL3, CCL4 and CCL5 have been found to block the entry of CCR5-tropic HIV into host cells and to suppress the viral replication in vitro, but the in vivo role of endogenous CC-chemokines in HIV-1 infection is still incompletely understood.


RESULTS
In this study, the primate host CCL3, CCL4 and CCL5 gene expression was evaluated in response to simian-human immunodeficiency virus (SHIV) infection in rhesus macaque model. Five rhesus macaques were inoculated with CCR5-tropic SHIV(SF162P4). The mRNA levels of CCL3, CCL4 and CCL5 were measured by real-time PCR at post inoculation day (PID) 0, 7, 14, 21, 35, 56 and 180 in peripheral blood. In addition, a selected subset of samples from CXCR4-tropic SHIV(Ku1)-infected macaques was included with objective to compare the differences in CC-chemokine down-regulation caused by the two SHIVs. Gut-associated lymphoid tissues (GALT) collected from SHIV(SF162P4)-infected animals were also tested by flow cytometry and confocal microscopy to corroborate the gene expression results. Predictably, higher viral loads and CD4+ T cell losses were observed at PID 14 in macaques infected with SHIV(Ku1) than with SHIV(SF162P4). A decline in CC-chemokine gene expression was also found during primary (PID 7-21), but not chronic (PID 180) stage of infection.


CONCLUSIONS
It was determined that A) SHIV(SF162P4) down-regulated the CC-chemokine gene expression during acute stage of infection to a greater extent (p<0.05) than SHIV(Ku1), and B) such down-regulation was not paralleled with the CD4+ T cell depletion. Evaluation of CC-chemokine enhancing immunomodulators such as synthetic CpG-oligonucleotides could be explored in future HIV vaccine studies.
Tulane National Primate Research Center, Covington, Louisiana, United States of America.
Wei
W
Zhao
Bapi
B
Pahar
Juan T
JT
Borda
Xavier
X
Alvarez
Karol
K
Sestak
D000818:Animals; D054405:Chemokine CCL3 / Q000235:genetics* / Q000276:immunology; D054407:Chemokine CCL4 / Q000235:genetics* / Q000276:immunology; D018946:Chemokine CCL5 / Q000235:genetics* / Q000276:immunology; D015536:Down-Regulation; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics / Q000276:immunology / Q000821:virology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5