Critical roles for both STAT1-dependent and STAT1-independent pathways in the control of primary dengue virus infection in mice.
Dengue virus (DEN), a flavivirus, causes dengue fever and dengue hemorrhagic fever/dengue shock syndrome, the most common mosquito-borne viral illnesses in humans worldwide. In this study, using STAT1(-/-) mice bearing two different mutant stat1 alleles in the 129/Sv/Ev background, we demonstrate that IFNR-dependent control of primary DEN infection involves both STAT1-dependent and STAT1-independent mechanisms. The STAT1 pathway is necessary for clearing the initial viral load, whereas the STAT1-independent pathway controls later viral burden and prevents DEN disease in mice. The STAT1-independent responses in mice with primary DEN infection included the early activation of B and NK cells as well as the up-regulation of MHC class I molecules on macrophages and dendritic cells. Infection of bone marrow-derived dendritic cell cultures with either DEN or Sindbis virus, another positive-strand RNA virus, confirmed the early vs late natures of the STAT1-dependent and STAT1-independent pathways. Collectively, these data begin to define the nature of the STAT1-dependent vs the STAT1-independent pathway in vivo.
Shresta
Sujan
S
Division of Infectious Diseases, School of Public Health, University of California, Berkeley, CA 94720, USA.
Sharar
Kristin L
KL
Prigozhin
Daniil M
DM
Snider
Heidi M
HM
Beatty
P Robert
PR
Harris
Eva
E
D000818:Animals; D001402:B-Lymphocytes / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus; D015395:Histocompatibility Antigens Class I; D007694:Killer Cells, Natural / Q000821:virology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000502:physiology; D050794:STAT1 Transcription Factor / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D019562:Viral Load
D015395:Histocompatibility Antigens Class I; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse