Natural killer (NK) cells are known for their ability to lyse tumour cell targets. Studies of infections by a number of viruses, including poxviruses and herpesviruses, have demonstrated that NK cells are vital for recovery from these infections. Little is known of the ability of viruses to infect and complete a productive replication cycle within NK cells. Even less is known concerning the effect of infection on NK cell biology. This study investigated the ability of ectromelia virus (ECTV) to infect NK cells in vitro and in vivo. Following ECTV infection, NK cell gamma interferon (IFN-γ) production was diminished and infected cells ceased proliferating and lost viability. ECTV infection of NK cells led to early and late virus gene expression and visualization of immature and mature virus particles, but no detectable increase in viable progeny virus. It was not unexpected that early gene expression occurred in infected NK cells, as the complete early transcription system is packaged within the virions. The detection of the secreted early virus-encoded immunomodulatory proteins IFN-γ-binding protein and ectromelia inhibitor of complement enzymes (EMICE) in NK cell culture supernatants suggests that even semi-permissive infection may permit immunomodulation of the local environment.
BaiH.,
BullerR. M.,
ChenN.,
GreenM.,
NuaraA. A.2005; Biosynthesis of the IFN- γ binding protein of ectromelia virus, the causative agent of mousepox. Virology 334:41–50[CrossRef]
BironC. A.,
ByronK. S.,
SullivanJ. L.1989; Severe herpesvirus infections in an adolescent without natural killer cells. N Engl J Med 320:1731–1735[CrossRef]
BrownM. G.,
DokunA. O.,
HeuselJ. W.,
SmithH. R.,
BeckmanD. L.,
BlattenbergerE. A.,
DubbeldeC. E.,
StoneL. R.,
ScalzoA. A.,
YokoyamaW. M.2001; Vital involvement of a natural killer cell activation receptor in resistance to viral infection. Science 292:934–937[CrossRef]
ChaudhriG.,
PanchanathanV.,
BullerR. M.,
van den EertweghA. J.,
ClaassenE.,
ZhouJ.,
de ChazalR.,
LamanJ. D.,
KarupiahG.2004; Polarized type 1 cytokine response and cell-mediated immunity determine genetic resistance to mousepox. Proc Natl Acad Sci U S A 101:9057–9062[CrossRef]
ChehimiJ.,
BandyopadhyayS.,
PrakashK.,
PerussiaB.,
HassanN. F.,
KawashimaH.,
CampbellD.,
KornbluthJ.,
StarrS. E.1991; In vitro infection of natural killer cells with different human immunodeficiency virus type 1 isolates. J Virol 65:1812–1822
ChenW.,
DrillienR.,
SpehnerD.,
BullerR. M.1992; Restricted replication of ectromelia virus in cell culture correlates with mutations in virus-encoded host range gene. Virology 187:433–442[CrossRef]
ChisholmS. E.,
ReyburnH. T.2006; Recognition of vaccinia virus-infected cells by human natural killer cells depends on natural cytotoxicity receptors. J Virol 80:2225–2233[CrossRef]
DanielsK. A.,
DevoraG.,
LaiW. C.,
O'DonnellC. L.,
BennettM.,
WelshR. M.2001; Murine cytomegalovirus is regulated by a discrete subset of natural killer cells reactive with monoclonal antibody to Ly49H. J Exp Med 194:29–44[CrossRef]
DelanoM. L.,
BrownsteinD. G.1995; Innate resistance to lethal mousepox is genetically linked to the NK gene complex on chromosome 6 and correlates with early restriction of virus replication by cells with an NK phenotype. J Virol 69:5875–5877
DrillienR.,
SpehnerD.,
BohbotA.,
HanauD.2000; Vaccinia virus-related events and phenotypic changes after infection of dendritic cells derived from human monocytes. Virology 268:471–481[CrossRef]
EarlP. L.,
MossB.,
WyattL. S.1998; Generation of recombinant vaccinia viruses. In Current Protocols in Molecular Biology pp. 16.17.1–16.17.19 Chichester, UK: Wiley;
EngelmayerJ.,
LarssonM.,
SubkleweM.,
ChahroudiA.,
CoxW. I.,
SteinmanR. M.,
BhardwajN.1999; Vaccinia virus inhibits the maturation of human dendritic cells: a novel mechanism of immune evasion. J Immunol 163:6762–6768
JacobyR. O.,
BhattP. N.,
BrownsteinD. G.1989; Evidence that NK cells and interferon are required for genetic resistance to lethal infection with ectromelia virus. Arch Virol 108:49–58[CrossRef]
JenneL.,
HauserC.,
ArrighiJ. F.,
SauratJ. H.,
HuginA. W.2000; Poxvirus as a vector to transduce human dendritic cells for immunotherapy: abortive infection but reduced APC function. Gene Ther 7:1575–1583[CrossRef]
KarupiahG.,
BullerR. M.,
Van RooijenN.,
DuarteC. J.,
ChenJ.1996; Different roles for CD4+ and CD8+ T lymphocytes and macrophage subsets in the control of a generalized virus infection. J Virol 70:8301–8309
KimS.,
Poursine-LaurentJ.,
TruscottS. M.,
LybargerL.,
SongY. J.,
YangL.,
FrenchA. R.,
SunwooJ. B.,
LemieuxS.other authors2005; Licensing of natural killer cells by host major histocompatibility complex class I molecules. Nature 436:709–713[CrossRef]
KirwanS.,
MerriamD.,
BarsbyN.,
McKinnonA.,
BurshtynD. N.2006; Vaccinia virus modulation of natural killer cell function by direct infection. Virology 347:75–87[CrossRef]
LiszewskiM. K.,
LeungM. K.,
HauhartR.,
BullerR. M.,
BertramP.,
WangX.,
RosengardA. M.,
KotwalG. J.,
AtkinsonJ. P.2006; Structure and regulatory profile of the monkeypox inhibitor of complement: comparison to homologs in vaccinia and variola and evidence for dimer formation. J Immunol 176:3725–3734[CrossRef]
ParkerA. K.,
ParkerS.,
YokoyamaW. M.,
CorbettJ. A.,
BullerR. M.2007; Induction of natural killer cell responses by ectromelia virus controls infection. J Virol 81:4070–4079[CrossRef]
PatelD. D.,
PickupD. J.,
JoklikW. K.1986; Isolation of cowpox virus A-type inclusions and characterization of their major protein component. Virology 149:174–189[CrossRef]
Sanchez-PuigJ. M.,
SanchezL.,
RoyG.,
BlascoR.2004; Susceptibility of different leukocyte cell types to vaccinia virus infection. Virol J 1:10[CrossRef]
ScalzoA. A.,
FitzgeraldN. A.,
SimmonsA.,
La VistaA. B.,
ShellamG. R.1990; Cmv-1, a genetic locus that controls murine cytomegalovirus replication in the spleen. J Exp Med 171:1469–1483[CrossRef]
SmithH. R.,
HeuselJ. W.,
MehtaI. K.,
KimS.,
DornerB. G.,
NaidenkoO. V.,
IizukaK.,
FurukawaH.,
BeckmanD. L.other authors2002; Recognition of a virus-encoded ligand by a natural killer cell activation receptor. Proc Natl Acad Sci U S A 99:8826–8831[CrossRef]