Mannan-binding lectin modulates the response to HSV-2 infection.
Viruses have developed numerous strategies to escape recognition by the immune system. However, some viruses such as herpes simplex virus-2 (HSV-2) are recognized by initiators of the complement system, e.g. mannan-binding lectin (MBL). To study the effects of MBL deficiency during viral infection we have chosen a model of generalized HSV-2 infection. We infected MBL-A and MBL-C double knock-out mice (DKO) with HSV-2 via the intraperitoneal (i.p.) route. DKO mice cleared HSV-2 from the liver less efficiently than the comparable wild-type animals. The impairment to effectively neutralize HSV-2 correlated with compromised liver function as measured by increased plasma levels of alanine-amino transferase. No differences in the viral burden were found in other organs such as spleen or brain. Thus, MBL-mediated protection was limited to the effects of preservation of liver homeostasis. Reconstitution with recombinant human MBL before and during the HSV-2 infection dramatically lowered the viral titres in the liver. Taken together, the data show that MBL modulates the response to HSV-2 in mice by affecting neutralization of the virus. To analyse if MBL plays a role in establishment and progression of human HSV-2 infection we analysed MBL levels in the serum samples from asymptomatic (virus-exposed people who have never displayed symptoms of HSV-2 infection) and symptomatic HSV-2 patients (people with recurrent HSV-2 infections). We found that the frequency of the MBL deficiency (<100 ng/ml) was higher in the symptomatic group and significantly different from that in the asymptomatic group (P = 0.0369). This suggests that lack of MBL-mediated complement activation increases susceptibility to viral infection.
Gadjeva
M
M
Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark. mg@immunology.au.dk
Paludan
S R
SR
Thiel
S
S
Slavov
V
V
Ruseva
M
M
Eriksson
K
K
Löwhagen
G-B
GB
Shi
L
L
Takahashi
K
K
Ezekowitz
A
A
Jensenius
J C
JC
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001921:Brain / Q000276:immunology; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology; D006561:Herpes Simplex / Q000097:blood / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D008099:Liver / Q000276:immunology; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology; D012008:Recurrence; D013154:Spleen / Q000276:immunology; D019562:Viral Load / Q000379:methods; D014764:Viral Proteins / Q000276:immunology
D037601:Mannose-Binding Lectin; D011994:Recombinant Proteins; D014764:Viral Proteins; D000410:Alanine Transaminase