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Chikungunya virus infection results in higher and persistent viral replication in aged rhesus macaques due to defects in anti-viral immunity.
PLoS Negl Trop Dis. 2013; 7(7):e2343.PN

Abstract

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne Alphavirus that causes a clinical disease involving fever, myalgia, nausea and rash. The distinguishing feature of CHIKV infection is the severe debilitating poly-arthralgia that may persist for several months after viral clearance. Since its re-emergence in 2004, CHIKV has spread from the Indian Ocean region to new locations including metropolitan Europe, Japan, and even the United States. The risk of importing CHIKV to new areas of the world is increasing due to high levels of viremia in infected individuals as well as the recent adaptation of the virus to the mosquito species Aedes albopictus. CHIKV re-emergence is also associated with new clinical complications including severe morbidity and, for the first time, mortality. In this study, we characterized disease progression and host immune responses in adult and aged Rhesus macaques infected with either the recent CHIKV outbreak strain La Reunion (LR) or the West African strain 37997. Our results indicate that following intravenous infection and regardless of the virus used, Rhesus macaques become viremic between days 1-5 post infection. While adult animals are able to control viral infection, aged animals show persistent virus in the spleen. Virus-specific T cell responses in the aged animals were reduced compared to adult animals and the B cell responses were also delayed and reduced in aged animals. Interestingly, regardless of age, T cell and antibody responses were more robust in animals infected with LR compared to 37997 CHIKV strain. Taken together these data suggest that the reduced immune responses in the aged animals promotes long-term virus persistence in CHIKV-LR infected Rhesus monkeys.

Authors+Show Affiliations

Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America. messaoud@ucr.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23936572

Citation

Messaoudi, Ilhem, et al. "Chikungunya Virus Infection Results in Higher and Persistent Viral Replication in Aged Rhesus Macaques Due to Defects in Anti-viral Immunity." PLoS Neglected Tropical Diseases, vol. 7, no. 7, 2013, pp. e2343.
Messaoudi I, Vomaske J, Totonchy T, et al. Chikungunya virus infection results in higher and persistent viral replication in aged rhesus macaques due to defects in anti-viral immunity. PLoS Negl Trop Dis. 2013;7(7):e2343.
Messaoudi, I., Vomaske, J., Totonchy, T., Kreklywich, C. N., Haberthur, K., Springgay, L., Brien, J. D., Diamond, M. S., Defilippis, V. R., & Streblow, D. N. (2013). Chikungunya virus infection results in higher and persistent viral replication in aged rhesus macaques due to defects in anti-viral immunity. PLoS Neglected Tropical Diseases, 7(7), e2343. https://doi.org/10.1371/journal.pntd.0002343
Messaoudi I, et al. Chikungunya Virus Infection Results in Higher and Persistent Viral Replication in Aged Rhesus Macaques Due to Defects in Anti-viral Immunity. PLoS Negl Trop Dis. 2013;7(7):e2343. PubMed PMID: 23936572.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chikungunya virus infection results in higher and persistent viral replication in aged rhesus macaques due to defects in anti-viral immunity. AU - Messaoudi,Ilhem, AU - Vomaske,Jennifer, AU - Totonchy,Thomas, AU - Kreklywich,Craig N, AU - Haberthur,Kristen, AU - Springgay,Laura, AU - Brien,James D, AU - Diamond,Michael S, AU - Defilippis,Victor R, AU - Streblow,Daniel N, Y1 - 2013/07/25/ PY - 2012/12/05/received PY - 2013/06/17/accepted PY - 2013/8/13/entrez PY - 2013/8/13/pubmed PY - 2014/2/8/medline SP - e2343 EP - e2343 JF - PLoS neglected tropical diseases JO - PLoS Negl Trop Dis VL - 7 IS - 7 N2 - Chikungunya virus (CHIKV) is a re-emerging mosquito-borne Alphavirus that causes a clinical disease involving fever, myalgia, nausea and rash. The distinguishing feature of CHIKV infection is the severe debilitating poly-arthralgia that may persist for several months after viral clearance. Since its re-emergence in 2004, CHIKV has spread from the Indian Ocean region to new locations including metropolitan Europe, Japan, and even the United States. The risk of importing CHIKV to new areas of the world is increasing due to high levels of viremia in infected individuals as well as the recent adaptation of the virus to the mosquito species Aedes albopictus. CHIKV re-emergence is also associated with new clinical complications including severe morbidity and, for the first time, mortality. In this study, we characterized disease progression and host immune responses in adult and aged Rhesus macaques infected with either the recent CHIKV outbreak strain La Reunion (LR) or the West African strain 37997. Our results indicate that following intravenous infection and regardless of the virus used, Rhesus macaques become viremic between days 1-5 post infection. While adult animals are able to control viral infection, aged animals show persistent virus in the spleen. Virus-specific T cell responses in the aged animals were reduced compared to adult animals and the B cell responses were also delayed and reduced in aged animals. Interestingly, regardless of age, T cell and antibody responses were more robust in animals infected with LR compared to 37997 CHIKV strain. Taken together these data suggest that the reduced immune responses in the aged animals promotes long-term virus persistence in CHIKV-LR infected Rhesus monkeys. SN - 1935-2735 UR - https://www.unboundmedicine.com/medline/citation/23936572/Chikungunya_virus_infection_results_in_higher_and_persistent_viral_replication_in_aged_rhesus_macaques_due_to_defects_in_anti_viral_immunity_ L2 - https://dx.plos.org/10.1371/journal.pntd.0002343 DB - PRIME DP - Unbound Medicine ER -