The viral chemokine MCK-2 of murine cytomegalovirus promotes infection as part of a gH/gL/MCK-2 complex.
Human cytomegalovirus (HCMV) forms two gH/gL glycoprotein complexes, gH/gL/gO and gH/gL/pUL(128,130,131A), which determine the tropism, the entry pathways and the mode of spread of the virus. For murine cytomegalovirus (MCMV), which serves as a model for HCMV, a gH/gL/gO complex functionally homologous to the HCMV gH/gL/gO complex has been described. Knock-out of MCMV gO does impair, but not abolish, virus spread indicating that also MCMV might form an alternative gH/gL complex. Here, we show that the MCMV CC chemokine MCK-2 forms a complex with the glycoprotein gH, a complex which is incorporated into the virion. We could additionally show that mutants lacking both, gO and MCK-2 are not able to produce infectious virus. Trans-complementation of these double mutants with either gO or MCK-2 showed that both proteins can promote infection of host cells, although through different entry pathways. MCK-2 has been extensively studied in vivo by others. It has been shown to be involved in attracting cells for virus dissemination and in regulating antiviral host responses. We now show that MCK-2, by forming a complex with gH, strongly promotes infection of macrophages in vitro and in vivo. Thus, MCK-2 may play a dual role in MCMV infection, as a chemokine regulating the host response and attracting specific target cells and as part of a glycoprotein complex promoting entry into cells crucial for virus dissemination.
Max von Pettenkofer-Institute for Virology, Ludwig-Maximilians-University Munich, Munich, Germany.
Felicia M
FM
Wagner
Ilija
I
Brizic
Adrian
A
Prager
Tihana
T
Trsan
Maja
M
Arapovic
Niels A W
NA
Lemmermann
Jürgen
J
Podlech
Matthias J
MJ
Reddehase
Frederic
F
Lemnitzer
Jens Bernhard
JB
Bosse
Martina
M
Gimpfl
Lisa
L
Marcinowski
Margaret
M
MacDonald
Heiko
H
Adler
Ulrich H
UH
Koszinowski
Barbara
B
Adler
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D007113:Immunity, Innate; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000821:virology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology / Q000821:virology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000276:immunology / Q000502:physiology*; D009154:Mutation; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000276:immunology / Q000502:physiology; D053586:Virus Internalization
D019742:Chemokines, CC; C121663:MCK-2 protein, Mouse cytomegalovirus 1; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins