TY - JOUR
T1 - Type I interferons and NK cells restrict gammaherpesvirus lymph node infection
AU - Lawler, Clara
AU - Tan, Cindy S.E.
AU - Simas, J. Pedro
AU - Stevenson, Philip G.
N1 - Funding Information:
This work, including the efforts of Philip G. Stevenson, was funded by Department of Health | National Health and Medical Research Council (NHMRC) (1060138, 1064015, and 1079180). This work, including the efforts of Philip G. Stevenson, was funded by Federaal Wetenschapsbeleid (BELSPO) (BELVIR). This work, including the efforts of J. Pedro Simas, was funded by Ministry of Education and Science | Fundação para a Ciência e a Tecnologia (FCT) (SFRH/BSAB/113927/2015). This work, including the efforts of Philip G. Stevenson, was funded by Australian Research Council (ARC) (FT130100138).
Publisher Copyright:
© 2016, American Society for Microbiology.
PY - 2016/10/15
Y1 - 2016/10/15
N2 - Gammaherpesviruses establish persistent, systemic infections and cause cancers. Murid herpesvirus 4 (MuHV-4) provides a unique window into the early events of host colonization. It spreads via lymph nodes. While dendritic cells (DC) pass MuHV-4 to lymph node B cells, subcapsular sinus macrophages (SSM), which capture virions from the afferent lymph, restrict its spread. Understanding how this restriction works offers potential clues to a more comprehensive defense. Type I interferon (IFN-I) blocked SSM lytic infection and reduced lytic cycle-independent viral reporter gene expression. Plasmacytoid DC were not required, but neither were SSM the only source of IFN-I, as IFN-I blockade increased infection in both intact and SSM-depleted mice. NK cells restricted lytic SSM infection independently of IFN-I, and SSM-derived virions spread to the spleen only when both IFN-I responses and NK cells were lacking. Thus, multiple innate defenses allowed SSM to adsorb virions from the afferent lymph with relative impunity. Enhancing IFN-I and NK cell recruitment could potentially also restrict DC infection and thus improve infection control.
AB - Gammaherpesviruses establish persistent, systemic infections and cause cancers. Murid herpesvirus 4 (MuHV-4) provides a unique window into the early events of host colonization. It spreads via lymph nodes. While dendritic cells (DC) pass MuHV-4 to lymph node B cells, subcapsular sinus macrophages (SSM), which capture virions from the afferent lymph, restrict its spread. Understanding how this restriction works offers potential clues to a more comprehensive defense. Type I interferon (IFN-I) blocked SSM lytic infection and reduced lytic cycle-independent viral reporter gene expression. Plasmacytoid DC were not required, but neither were SSM the only source of IFN-I, as IFN-I blockade increased infection in both intact and SSM-depleted mice. NK cells restricted lytic SSM infection independently of IFN-I, and SSM-derived virions spread to the spleen only when both IFN-I responses and NK cells were lacking. Thus, multiple innate defenses allowed SSM to adsorb virions from the afferent lymph with relative impunity. Enhancing IFN-I and NK cell recruitment could potentially also restrict DC infection and thus improve infection control.
UR - http://www.scopus.com/inward/record.url?scp=84990068723&partnerID=8YFLogxK
U2 - 10.1128/JVI.01108-16
DO - 10.1128/JVI.01108-16
M3 - Article
C2 - 27466430
AN - SCOPUS:84990068723
SN - 0022-538X
VL - 90
SP - 9046
EP - 9057
JO - Journal of Virology
JF - Journal of Virology
IS - 20
ER -
