PMID- 25056886
OWN - NLM
STAT- MEDLINE
DCOM- 20141111
LR  - 20211021
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 88
IP  - 19
DP  - 2014 Oct
TI  - Antiviral regulation in porcine monocytic cells at different activation states.
PG  - 11395-410
LID - 10.1128/JVI.01714-14 [doi]
AB  - Monocytic cells, including macrophages and dendritic cells, exist in different 
      activation states that are critical to the regulation of antimicrobial immunity. 
      Many pandemic viruses are monocytotropic, including porcine reproductive and 
      respiratory syndrome virus (PRRSV), which directly infects subsets of monocytic 
      cells and interferes with antiviral responses. To study antiviral responses in 
      PRRSV-infected monocytic cells, we characterized inflammatory cytokine responses 
      and genome-wide profiled signature genes to investigate response pathways in 
      uninfected and PRRSV-infected monocytic cells at different activation states. Our 
      findings showed suppressed interferon (IFN) production in macrophages in 
      non-antiviral states and an arrest of lipid metabolic pathways in macrophages at 
      antiviral states. Importantly, porcine monocytic cells at different activation 
      states were susceptible to PRRSV and responded differently to viral infection. 
      Based on Gene Ontology (GO) analysis, two approaches were used to potentiate 
      antiviral activity: (i) pharmaceutical modulation of cellular lipid metabolism 
      and (ii) in situ PRRSV replication-competent expression of interferon alpha 
      (IFN-alpha). Both approaches significantly suppressed exogenous viral infection in 
      monocytic cells. In particular, the engineered IFN-expressing PRRSV strain 
      eliminated exogenous virus infection and sustained cell viability at 4 days 
      postinfection in macrophages. These findings suggest an intricate interaction of 
      viral infection with the activation status of porcine monocytic cells. An 
      understanding and integration of antiviral infection with activation status of 
      monocytic cells may provide a means of potentiating antiviral immunity. 
      IMPORTANCE: Activation statuses of monocytic cells, including monocytes, 
      macrophages (Mvarphis), and dendritic cells (DCs), are critically important for 
      antiviral immunity. Unfortunately, the activation status of porcine monocytic 
      cells or how cell activation status functionally interacts with antiviral 
      immunity remains largely unknown. This is a significant omission because many 
      economically important porcine viruses are monocytotropic, including our focus, 
      PRRSV, which alone causes nearly $800 million economic loss annually in the U.S. 
      swine industries. PRRSV is ideal for deciphering how monocytic cell activation 
      statuses interact with antiviral immunity, because it directly infects subsets of 
      monocytic cells and subverts overall immune responses. In this study, we 
      systematically investigate the activation status of porcine monocytic cells to 
      determine the intricate interaction of viral infection with activation statuses 
      and functionally regulate antiviral immunity within the framework of the 
      activation paradigm. Our findings may provide a means of potentiating antiviral 
      immunity and leading to novel vaccines for PRRS prevention.
CI  - Copyright (c) 2014, American Society for Microbiology. All Rights Reserved.
FAU - Sang, Yongming
AU  - Sang Y
AD  - Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas 
      State University, Manhattan, Kansas, USA ysang@vet.k-state.edu 
      blecha@vet.k-state.edu.
FAU - Rowland, Raymond R R
AU  - Rowland RR
AD  - Department of Diagnostic Medicine and Pathobiology, College of Veterinary 
      Medicine, Kansas State University, Manhattan, Kansas, USA.
FAU - Blecha, Frank
AU  - Blecha F
AD  - Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas 
      State University, Manhattan, Kansas, USA ysang@vet.k-state.edu 
      blecha@vet.k-state.edu.
LA  - eng
GR  - P20 RR017686/RR/NCRR NIH HHS/United States
GR  - P20-RR017686/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20140723
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Interferon-alpha)
SB  - IM
MH  - Animals
MH  - Dendritic Cells/*immunology/virology
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation
MH  - Host-Pathogen Interactions
MH  - Immunity, Cellular
MH  - Interferon-alpha/biosynthesis/immunology
MH  - Lipid Metabolism/immunology
MH  - Molecular Sequence Annotation
MH  - Monocytes/*immunology/virology
MH  - Porcine Reproductive and Respiratory Syndrome/*immunology/virology
MH  - Porcine respiratory and reproductive syndrome virus/*immunology
MH  - Swine
PMC - PMC4178830
EDAT- 2014/07/25 06:00
MHDA- 2014/11/12 06:00
PMCR- 2015/04/01
CRDT- 2014/07/25 06:00
PHST- 2014/07/25 06:00 [entrez]
PHST- 2014/07/25 06:00 [pubmed]
PHST- 2014/11/12 06:00 [medline]
PHST- 2015/04/01 00:00 [pmc-release]
AID - JVI.01714-14 [pii]
AID - 01714-14 [pii]
AID - 10.1128/JVI.01714-14 [doi]
PST - ppublish
SO  - J Virol. 2014 Oct;88(19):11395-410. doi: 10.1128/JVI.01714-14. Epub 2014 Jul 23.