Within-host viral dynamics of dengue serotype 1 infection

被引:87
作者
Clapham, Hannah E. [1 ]
Tricou, Vianney [2 ]
Nguyen Van Vinh Chau [3 ]
Simmons, Cameron P. [4 ,5 ,6 ]
Ferguson, Neil M. [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, MRC, Ctr Outbreak Anal & Modelling, London W2 1PG, England
[2] Inst Pasteur, Bangui, Cent Afr Republ
[3] Hosp Trop Dis, Ho Chi Minh City, Vietnam
[4] Univ Oxford, Clin Res Unit, Ho Chi Minh City, Vietnam
[5] Univ Oxford, Nuffield Dept Med, Ctr Trop Med, Oxford OX1 2JD, England
[6] Univ Melbourne, Nossal Inst Global Hlth, Melbourne, Vic 3010, Australia
基金
英国惠康基金;
关键词
dengue; virus dynamics; within-host modelling; ANTIBODY-DEPENDENT ENHANCEMENT; ADAPTIVE IMMUNE-RESPONSE; VIRUS-INFECTION; HEMORRHAGIC-FEVER; HUMAN-MONOCYTES; CELL RESPONSES; DV INFECTION; T-CELLS; VIREMIA; KINETICS;
D O I
10.1098/rsif.2014.0094
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Dengue, the most common mosquito-borne viral infection of humans, is endemic across much of the world, including much of tropical Asia and is increasing in its geographical range. Here, we present a mathematical model of dengue virus dynamics within infected individuals, detailing the interaction between virus and a simple immune response. We fit this model to measurements of plasma viral titre from cases of primary and secondary DENV 1 infection in Vietnam. We show that variation in model parameters governing the immune response is sufficient to create the observed variation in virus dynamics between individuals. Estimating model parameter values, we find parameter differences between primary and secondary cases consistent with the theory of antibody-dependent enhancement (namely enhanced rates of viral entry to target cells in secondary cases). Finally, we use our model to examine the potential impact of an antiviral drug on the within-host dynamics of dengue. We conclude that the impact of antiviral therapy on virus dynamics is likely to be limited if therapy is only started at the onset of symptoms, owing to the typically late stage of viral pathogenesis reached by the time symptoms are manifested and thus treatment is started.
引用
收藏
页数:11
相关论文
共 52 条
[1]  
[Anonymous], 2012, R LANG ENV STAT COMP
[2]   Kinetics of influenza A virus infection in humans [J].
Baccam, Prasith ;
Beauchemin, Catherine ;
Macken, Catherine A. ;
Hayden, Frederick G. ;
Perelson, Alan S. .
JOURNAL OF VIROLOGY, 2006, 80 (15) :7590-7599
[3]   The Human Immune Response to Dengue Virus Is Dominated by Highly Cross-Reactive Antibodies Endowed with Neutralizing and Enhancing Activity [J].
Beltramello, Martina ;
Williams, Katherine L. ;
Simmons, Cameron P. ;
Macagno, Annalisa ;
Simonelli, Luca ;
Quyen, Nguyen Than Ha ;
Sukupolvi-Petty, Soila ;
Navarro-Sanchez, Erika ;
Young, Paul R. ;
de Silva, Aravinda M. ;
Rey, Felix A. ;
Varani, Luca ;
Whitehead, Stephen S. ;
Diamond, Michael S. ;
Harris, Eva ;
Lanzavecchia, Antonio ;
Sallusto, Federica .
CELL HOST & MICROBE, 2010, 8 (03) :271-283
[4]   The global distribution and burden of dengue [J].
Bhatt, Samir ;
Gething, Peter W. ;
Brady, Oliver J. ;
Messina, Jane P. ;
Farlow, Andrew W. ;
Moyes, Catherine L. ;
Drake, John M. ;
Brownstein, John S. ;
Hoen, Anne G. ;
Sankoh, Osman ;
Myers, Monica F. ;
George, Dylan B. ;
Jaenisch, Thomas ;
Wint, G. R. William ;
Simmons, Cameron P. ;
Scott, Thomas W. ;
Farrar, Jeremy J. ;
Hay, Simon I. .
NATURE, 2013, 496 (7446) :504-507
[5]   Antibody-dependent enhancement in dengue virus infections [J].
Burke, DS ;
Kliks, S .
JOURNAL OF INFECTIOUS DISEASES, 2006, 193 (04) :601-603
[6]   American genotype structures decrease dengue virus output from human monocytes and dendritic cells [J].
Cologna, R ;
Rico-Hesse, R .
JOURNAL OF VIROLOGY, 2003, 77 (07) :3929-3938
[7]   The WHO dengue classification and case definitions: time for a reassessment [J].
Deen, Jacqueline L. ;
Harris, Eva ;
Wills, Bridget ;
Balmaseda, Angel ;
Hammond, Samantha Nadia ;
Rocha, Crisanta ;
Dung, Nguyen Minh ;
Hung, Nguyen Thanh ;
Hien, Tran Tinh ;
Farrar, Jeremy J. .
LANCET, 2006, 368 (9530) :170-173
[8]   Cross-Reacting Antibodies Enhance Dengue Virus Infection in Humans [J].
Dejnirattisai, Wanwisa ;
Jumnainsong, Amonrat ;
Onsirisakul, Naruthai ;
Fitton, Patricia ;
Vasanawathana, Sirijitt ;
Limpitikul, Wannee ;
Puttikhunt, Chunya ;
Edwards, Carolyn ;
Duangchinda, Thaneeya ;
Supasa, Sunpetchuda ;
Chawansuntati, Kriangkrai ;
Malasit, Prida ;
Mongkolsapaya, Juthathip ;
Screaton, Gavin .
SCIENCE, 2010, 328 (5979) :745-748
[9]   Kinetics of Plasma Viremia and Soluble Nonstructural Protein 1 Concentrations in Dengue: Differential Effects According to Serotype and Immune Status [J].
Duyen, Huynh T. L. ;
Ngoc, Tran V. ;
Ha, Do T. ;
Hang, Vu T. T. ;
Kieu, Nguyen T. T. ;
Young, Paul R. ;
Farrar, Jeremy J. ;
Simmons, Cameron P. ;
Wolbers, Marcel ;
Wills, Bridget A. .
JOURNAL OF INFECTIOUS DISEASES, 2011, 203 (09) :1292-1300
[10]   Relationship of preexisting dengue virus (DV) neutralizing antibody levels to viremia and severity of disease in a prospective cohort study of DV infection in Thailand [J].
Endy, TP ;
Nisalak, A ;
Chunsuttitwat, S ;
Vaughn, DW ;
Green, S ;
Ennis, FA ;
Rothman, AL ;
Libraty, DH .
JOURNAL OF INFECTIOUS DISEASES, 2004, 189 (06) :990-1000