PMID- 15498041 OWN - NLM STAT- MEDLINE DCOM- 20041214 LR - 20181113 IS - 0009-9104 (Print) IS - 1365-2249 (Electronic) IS - 0009-9104 (Linking) VI - 138 IP - 2 DP - 2004 Nov TI - Mannan-binding lectin modulates the response to HSV-2 infection. PG - 304-11 AB - 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. FAU - Gadjeva, M AU - Gadjeva M AD - Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark. mg@immunology.au.dk FAU - Paludan, S R AU - Paludan SR FAU - Thiel, S AU - Thiel S FAU - Slavov, V AU - Slavov V FAU - Ruseva, M AU - Ruseva M FAU - Eriksson, K AU - Eriksson K FAU - Lowhagen, G-B AU - Lowhagen GB FAU - Shi, L AU - Shi L FAU - Takahashi, K AU - Takahashi K FAU - Ezekowitz, A AU - Ezekowitz A FAU - Jensenius, J C AU - Jensenius JC LA - eng PT - Journal Article PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (Mannose-Binding Lectin) RN - 0 (Recombinant Proteins) RN - 0 (Viral Proteins) RN - EC 2.6.1.2 (Alanine Transaminase) SB - IM MH - Adult MH - Aged MH - Alanine Transaminase/blood MH - Animals MH - Brain/immunology MH - Female MH - Herpes Genitalis/immunology MH - Herpes Simplex/blood/*immunology MH - Herpesvirus 2, Human/*immunology MH - Homeostasis/immunology MH - Humans MH - Liver/immunology MH - Male MH - Mannose-Binding Lectin/blood/*immunology MH - Mice MH - Mice, Knockout MH - Middle Aged MH - Recombinant Proteins/immunology MH - Recurrence MH - Spleen/immunology MH - Viral Load/methods MH - Viral Proteins/immunology PMC - PMC1809223 EDAT- 2004/10/23 09:00 MHDA- 2004/12/16 09:00 PMCR- 2005/11/01 CRDT- 2004/10/23 09:00 PHST- 2004/10/23 09:00 [pubmed] PHST- 2004/12/16 09:00 [medline] PHST- 2004/10/23 09:00 [entrez] PHST- 2005/11/01 00:00 [pmc-release] AID - CEI2616 [pii] AID - 10.1111/j.1365-2249.2004.02616.x [doi] PST - ppublish SO - Clin Exp Immunol. 2004 Nov;138(2):304-11. doi: 10.1111/j.1365-2249.2004.02616.x.