Alternative entry receptors for herpes simplex virus and their roles in disease.
Either herpesvirus entry mediator (HVEM, TNFRSF14) or nectin-1 (PVRL1) is sufficient for herpes simplex virus (HSV) infection of cultured cells. The contribution of individual receptors to infection in vivo and to disease is less clear. To assess this, Tnfrsf14(-/-) and/or Pvrl1(-/-) mice were challenged intravaginally with HSV-2. Infection of the vaginal epithelium occurred in the absence of either HVEM or nectin-1 but was virtually undetectable when both receptors were absent, indicating that either HVEM or nectin-1 was necessary. Absence of nectin-1 (but not HVEM) reduced efficiency of infection of the vaginal epithelium and viral spread to the nervous system, attenuating neurological disease and preventing external lesion development. While nectin-1 proved not to be essential for infection of the nervous system, it is required for the full manifestations of disease. This study illustrates the value of mutant mice for understanding receptor contributions to disease caused by a human virus.
Taylor
Joann M
JM
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Lin
Erick
E
Susmarski
Nanette
N
Yoon
Miri
M
Zago
Anna
A
Ware
Carl F
CF
Pfeffer
Klaus
K
Miyoshi
Jun
J
Takai
Yoshimi
Y
Spear
Patricia G
PG
D000818:Animals; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006561:Herpes Simplex / Q000235:genetics / Q000503:physiopathology* / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D000075983:Nectins; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000172:deficiency / Q000235:genetics; D011991:Receptors, Virus / Q000502:physiology*; D018139:Simplexvirus / Q000235:genetics / Q000472:pathogenicity*; D014621:Vagina / Q000821:virology
D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; C000619015:Nectin1 protein, mouse; D000075983:Nectins; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C506029:Tnfrsf14 protein, mouse