Abstract
While CD8+ T cells are clearly important in controlling virus replication during HIV and SIV infections, the mechanisms underlying this antiviral effect remain poorly understood. In this study, we assessed the in vivo effect of CD8+ lymphocyte depletion on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques. We treated two groups of animals that were either CD8+ lymphocyte-depleted or controls with antiretroviral therapy, and used mathematical modeling to assess the lifespan of infected cells either in the presence or absence of CD8+ lymphocytes. We found that, in both early (day 57 post-SIV) and late (day 177 post-SIV) chronic SIV infection, depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of either short- or long-lived productively infected cells in vivo. This result indicates that the presence of CD8+ lymphocytes does not result in a noticeably shorter lifespan of productively SIVinfected cells, and thus that direct cell killing is unlikely to be the main mechanism underlying the antiviral effect of CD8+ T cells in SIV-infected macaques with high virus replication.
| Original language | English (US) |
|---|---|
| Article number | e1000747 |
| Journal | PLoS Pathogens |
| Volume | 6 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2010 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Parasitology
- Microbiology
- Immunology
- Molecular Biology
- Genetics
- Virology
Cite this
CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells. / Klatt, Nichole; Shudo, Emi; Ortiz, Alex M.; Engram, Jessica C.; Paiardini, Mirko; Lawson, Benton; Miller, Michael D.; Else, James; Pandrea, Ivona; Estes, Jacob D.; Apetrei, Cristian; Schmitz, Joern E.; Ribeiro, Ruy M.; Perelson, Alan S.; Silvestri, Guido.
In: PLoS Pathogens, Vol. 6, No. 1, e1000747, 01.01.2010.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells
AU - Klatt, Nichole
AU - Shudo, Emi
AU - Ortiz, Alex M.
AU - Engram, Jessica C.
AU - Paiardini, Mirko
AU - Lawson, Benton
AU - Miller, Michael D.
AU - Else, James
AU - Pandrea, Ivona
AU - Estes, Jacob D.
AU - Apetrei, Cristian
AU - Schmitz, Joern E.
AU - Ribeiro, Ruy M.
AU - Perelson, Alan S.
AU - Silvestri, Guido
PY - 2010/1/1
Y1 - 2010/1/1
N2 - While CD8+ T cells are clearly important in controlling virus replication during HIV and SIV infections, the mechanisms underlying this antiviral effect remain poorly understood. In this study, we assessed the in vivo effect of CD8+ lymphocyte depletion on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques. We treated two groups of animals that were either CD8+ lymphocyte-depleted or controls with antiretroviral therapy, and used mathematical modeling to assess the lifespan of infected cells either in the presence or absence of CD8+ lymphocytes. We found that, in both early (day 57 post-SIV) and late (day 177 post-SIV) chronic SIV infection, depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of either short- or long-lived productively infected cells in vivo. This result indicates that the presence of CD8+ lymphocytes does not result in a noticeably shorter lifespan of productively SIVinfected cells, and thus that direct cell killing is unlikely to be the main mechanism underlying the antiviral effect of CD8+ T cells in SIV-infected macaques with high virus replication.
AB - While CD8+ T cells are clearly important in controlling virus replication during HIV and SIV infections, the mechanisms underlying this antiviral effect remain poorly understood. In this study, we assessed the in vivo effect of CD8+ lymphocyte depletion on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques. We treated two groups of animals that were either CD8+ lymphocyte-depleted or controls with antiretroviral therapy, and used mathematical modeling to assess the lifespan of infected cells either in the presence or absence of CD8+ lymphocytes. We found that, in both early (day 57 post-SIV) and late (day 177 post-SIV) chronic SIV infection, depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of either short- or long-lived productively infected cells in vivo. This result indicates that the presence of CD8+ lymphocytes does not result in a noticeably shorter lifespan of productively SIVinfected cells, and thus that direct cell killing is unlikely to be the main mechanism underlying the antiviral effect of CD8+ T cells in SIV-infected macaques with high virus replication.
UR - http://www.scopus.com/inward/record.url?scp=77649217418&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77649217418&partnerID=8YFLogxK
U2 - 10.1371/journal.ppat.1000747
DO - 10.1371/journal.ppat.1000747
M3 - Article
C2 - 20126441
AN - SCOPUS:77649217418
VL - 6
JO - PLoS Pathogens
JF - PLoS Pathogens
SN - 1553-7366
IS - 1
M1 - e1000747
ER -