The role of signal transducer and activator of transcription 3 in Rift Valley fever virus infection.
Rift Valley fever (RVF) is a zoonotic disease that can cause severe illness in humans and livestock, triggering spontaneous abortion in almost 100% of pregnant ruminants. In this study, we demonstrate that signal transducer and activator of transcription 3 (STAT3) is phosphorylated on its conserved tyrosine residue (Y705) following RVFV infection. This phosphorylation was dependent on a major virulence factor, the viral nonstructural protein NSs. Loss of STAT3 had little effect on viral replication, but rather resulted in cells being more susceptible to RVFV-induced cell death. Phosphorylated STAT3 translocated to the nucleus, coinciding with inhibition of fos, jun, and nr4a2 gene expression, and the presence of STAT3 and NSs at the nr4a2 promoter. NSs was found predominantly in the cytoplasm of STAT3 null cells, indicating that STAT3 influences NSs nuclear localization. Collectively, these data demonstrate that STAT3 functions in a pro-survival capacity through modulation of NSs localization.
National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA, United States.
Chelsea
C
Pinkham
National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA, United States.
Soyeon
S
An
National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA, United States.
Lindsay
L
Lundberg
National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA, United States.
Neha
N
Bansal
National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA, United States.
Ashwini
A
Benedict
National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA, United States.
Aarthi
A
Narayanan
National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA, United States. Electronic address: kkehnhal@gmu.edu.
Kylene
K
Kehn-Hall
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006801:Humans; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021381:Protein Transport; D012295:Rift Valley Fever / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D012296:Rift Valley fever virus / Q000187:drug effects / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014779:Virus Replication
D051017:Apoptosis Regulatory Proteins; D050796:STAT3 Transcription Factor; D017361:Viral Nonstructural Proteins; D014443:Tyrosine
Apoptosis; NR4A2; NSs; RVFV; Rift Valley fever virus; STAT; STAT3; Signal transducer and activator of transcription