Mannose-binding lectin in severe acute respiratory syndrome coronavirus infection

Little is known about the innate immune response to severe acute respiratory syndrome (SARS) coronavirus (CoV) infection. Mannose-binding lectin (MBL), a key molecule in innate immunity, functions as an ante-antibody before the specific antibody response. Here, we describe a case-control study that included 569 patients with SARS and 1188 control subjects and used in vitro assays to investigate the role that MBL plays in SARS-CoV infection. The distribution of MBL gene polymorphisms was significantly different between patients with SARS and control subjects, with a higher frequency of haplotypes associated with low or deficient serum levels of MBL in patients with SARS than in control subjects. Serum levels of MBL were also significantly lower in patients with SARS than in control subjects. There was, however, no association between MBL genotypes, which are associated with low or deficient serum levels of MBL, and mortality related to SARS. MBL could bind SARS-CoV in a dose- and calcium-dependent and mannan-inhibitable fashion in vitro, suggesting that binding is through the carbohydrate recognition domains of MBL. Furthermore, deposition of complement C4 on SARS-CoV was enhanced by MBL. Inhibition of the infectivity of SARS-CoV by MBL in fetal rhesus kidney cells (FRhK-4) was also observed. These results suggest that MBL contributes to the first-line host defense against SARS-CoV and that MBL deficiency is a susceptibility factor for acquisition of SARS. © 2005 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

Zika beyond the Americas: Travelers as sentinels of Zika virus transmission. A GeoSentinel analysis, 2012 to 2016.

Background: Zika virus (ZIKV) was first isolated in Africa; decades later, caused large outbreaks in the Pacific, and is considered endemic in Asia. We aim to describe ZIKV disease epidemiology outside the Americas, the importance of travelers as sentinels of disease transmission, and discrepancies in travel advisories from major international health organizations. Methods and findings This descriptive analysis using GeoSentinel Surveillance Network records involves sixty-four travel and tropical medicine clinics in 29 countries. Ill returned travelers with a confirmed or probable diagnosis of ZIKV disease acquired in Africa, Asia and the Pacific seen between 1 January 2012 and 31 December 2016 are included, and the frequencies of demographic, trip, and diagnostic characteristics described. ZIKV was acquired in Asia (18), the Pacific (10) and Africa (1). For five countries (Indonesia, Philippines, Thailand, Vietnam, Cameroon), GeoSentinel patients were sentinel markers of recent Zika activity. Additionally, the first confirmed ZIKV infection acquired in Kiribati was reported to GeoSentinel (2015), and a probable case was reported from Timor Leste (April 2016), representing the only case known to date. Review of Zika situation updates from major international health authorities for country risk classifications shows heterogeneity in ZIKV country travel advisories. Conclusions: Travelers are integral to the global spread of ZIKV, serving as sentinel markers of disease activity. Although GeoSentinel data are collected by specialized clinics and do not capture all imported cases, we show that surveillance of imported infections by returned travelers augments local surveillance system data regarding ZIKV epidemiology and can assist with risk categorization by international authorities. However, travel advisories are variable due to risk uncertainties

Primary structure of bovine collectin-43 (CL-43). Comparison with conglutinin and lung surfactant protein-D

Collectin-43 (CL-43) is a bovine serum protein that is composed of subunits of three identical chains, each of which contains a collagen region and a C-type carbohydrate recognition domain; thus, CL-43 belongs to the collectins (group III of the C-type lectins). We have derived the complete primary sequence of CL-43 using partial protein sequencing, cDNA cloning, and reverse transcription-polymerase chain reaction techniques. The primary sequence of CL-43 shows that it contains an N-terminal region of 28 residues, followed by a collagenous domain of 38 repeats of Gly-Xaa-Yaa and then a C- terminal section of 159 residues, containing a short 'neck' region and the carbohydrate recognition domain with the conserved residues found in all C- type lectins. The amino acid sequence of CL-43 showed 74% identity to bovine conglutinin and 70% identity to bovine lung surfactant protein D (SP-D), but the collagen region is considerably shorter than the 57 Gly-Xaa-Yaa triplets found in conglutinin and SP-D. Northern blot analysis showed that CL-43 was only synthesized in bovine liver, with no detectable signal in a variety of other bovine tissues, including lung. No cross-hybridizing signals were detected in mRNA from sheep, human, rat, or mouse liver. Since CL-43 and conglutinin have only been detected in members of bovidae, it is probable that an ancestral gene of these two proteins was first derived from a SP-D- like gene, and that this ancestral gene duplicated during evolution.published_or_final_versio

Activation of the lectin pathway by natural IgM in a model of ischemia/reperfusion injury

Reperfusion of ischemic tissues elicits an acute inflammatory response involving serum complement, which is activated by circulating natural IgM specific to self-Ags exposed by ischemia. Recent reports demonstrating a role for the lectin pathway raise a question regarding the initial events in complement activation. To dissect the individual roles of natural IgM and lectin in activation of complement, mice bearing genetic deficiency in early complement, IgM, or mannan-binding lectin were characterized in a mesenteric model of ischemia reperfusion injury. The results reveal that IgM binds initially to ischemic Ag providing a binding site for mannan-binding lectin which subsequently leads to activation of complement and injury