Abstract
| Original language | English |
|---|---|
| Article number | e1003834 |
| Number of pages | 15 |
| Journal | PLoS Pathogens |
| Volume | 9 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2013 |
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An in-depth comparison of latent HIV-1 reactivation in multiple cell model systems and resting CD4+ T cells from aviremic patients. / Spina, Celsa A; Anderson, Jenny; Archin, Nancie M; Bosque, Alberto; Chan, Jonathan; Famiglietti, Marylinda; Green, Warner; Kashuba, Angela; Lewin, Sharon R; Margolis, David M; Mau, Matthew; Ruelas, Debbie; Saleh, Suha; Shirakawa, Kotaro; Siliciano, Robert F; Singhania, Akul; Soto, Paula; Terry, Valeri H; Verdin, Eric; Woelk, Christopher; Wooden, Stacey; Xing, Sifei; Planelles, Vicente.
In: PLoS Pathogens, Vol. 9, No. 12, e1003834, 2013.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - An in-depth comparison of latent HIV-1 reactivation in multiple cell model systems and resting CD4+ T cells from aviremic patients
AU - Spina, Celsa A
AU - Anderson, Jenny
AU - Archin, Nancie M
AU - Bosque, Alberto
AU - Chan, Jonathan
AU - Famiglietti, Marylinda
AU - Green, Warner
AU - Kashuba, Angela
AU - Lewin, Sharon R
AU - Margolis, David M
AU - Mau, Matthew
AU - Ruelas, Debbie
AU - Saleh, Suha
AU - Shirakawa, Kotaro
AU - Siliciano, Robert F
AU - Singhania, Akul
AU - Soto, Paula
AU - Terry, Valeri H
AU - Verdin, Eric
AU - Woelk, Christopher
AU - Wooden, Stacey
AU - Xing, Sifei
AU - Planelles, Vicente
PY - 2013
Y1 - 2013
N2 - The possibility of HIV-1 eradication has been limited by the existence of latently infected cellular reservoirs. Studies to examine control of HIV latency and potential reactivation have been hindered by the small numbers of latently infected cells found in vivo. Major conceptual leaps have been facilitated by the use of latently infected T cell lines and primary cells. However, notable differences exist among cell model systems. Furthermore, screening efforts in specific cell models have identified drug candidates for ?anti-latency? therapy, which often fail to reactivate HIV uniformly across different models. Therefore, the activity of a given drug candidate, demonstrated in a particular cellular model, cannot reliably predict its activity in other cell model systems or in infected patient cells, tested ex vivo. This situation represents a critical knowledge gap that adversely affects our ability to identify promising treatment compounds and hinders the advancement of drug testing into relevant animal models and clinical trials. To begin to understand the biological characteristics that are inherent to each HIV-1 latency model, we compared the response properties of five primary T cell models, four J-Lat cell models and those obtained with a viral outgrowth assay using patient-derived infected cells. A panel of thirteen stimuli that are known to reactivate HIV by defined mechanisms of action was selected and tested in parallel in all models. Our results indicate that no single in vitro cell model alone is able to capture accurately the ex vivo response characteristics of latently infected T cells from patients. Most cell models demonstrated that sensitivity to HIV reactivation was skewed toward or against specific drug classes. Protein kinase C agonists and PHA reactivated latent HIV uniformly across models, although drugs in most other classes did not.
AB - The possibility of HIV-1 eradication has been limited by the existence of latently infected cellular reservoirs. Studies to examine control of HIV latency and potential reactivation have been hindered by the small numbers of latently infected cells found in vivo. Major conceptual leaps have been facilitated by the use of latently infected T cell lines and primary cells. However, notable differences exist among cell model systems. Furthermore, screening efforts in specific cell models have identified drug candidates for ?anti-latency? therapy, which often fail to reactivate HIV uniformly across different models. Therefore, the activity of a given drug candidate, demonstrated in a particular cellular model, cannot reliably predict its activity in other cell model systems or in infected patient cells, tested ex vivo. This situation represents a critical knowledge gap that adversely affects our ability to identify promising treatment compounds and hinders the advancement of drug testing into relevant animal models and clinical trials. To begin to understand the biological characteristics that are inherent to each HIV-1 latency model, we compared the response properties of five primary T cell models, four J-Lat cell models and those obtained with a viral outgrowth assay using patient-derived infected cells. A panel of thirteen stimuli that are known to reactivate HIV by defined mechanisms of action was selected and tested in parallel in all models. Our results indicate that no single in vitro cell model alone is able to capture accurately the ex vivo response characteristics of latently infected T cells from patients. Most cell models demonstrated that sensitivity to HIV reactivation was skewed toward or against specific drug classes. Protein kinase C agonists and PHA reactivated latent HIV uniformly across models, although drugs in most other classes did not.
UR - http://www.scopus.com/inward/record.url?scp=84892845657&partnerID=8YFLogxK
U2 - 10.1371/journal.ppat.1003834
DO - 10.1371/journal.ppat.1003834
M3 - Article
VL - 9
JO - PLoS Pathogens
JF - PLoS Pathogens
SN - 1553-7366
IS - 12
M1 - e1003834
ER -