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The pestivirus bovine viral diarrhea virus (BVDV) was shown to bind to the bovine CD46 molecule, which subsequently promotes entry of the virus. To assess the receptor usage of BVDV type 1 (BVDV-1) and BVDV-2, 30 BVDV isolates including clinical samples were assayed for their sensitivity to anti-CD46 antibodies. With a single exception the infectivity of all tested strains of BVDV-1 and BVDV-2 was inhibited by anti-CD46 antibodies, which indicates the general usage of CD46 as a BVDV receptor. Molecular analysis of the interaction between CD46 and the BVD virion was performed by mapping the virus binding site on the CD46 molecule. Single complement control protein modules (CCPs) within the bovine CD46 were either deleted or replaced by analogous CCPs of porcine CD46, which does not bind BVDV. While the epitopes recognized by anti-CD46 monoclonal antibodies which block BVDV infection were attributed to CCP1 and CCP2, in functional assays only CCP1 turned out to be essential for BVDV binding and infection. Within CCP1 two short peptides on antiparallel beta strands were identified as crucial for the binding of BVDV. Exchanges of these two peptide sequences were sufficient for a loss of function in bovine CD46 as well as a gain of function in porcine CD46. Determination of the size constraints of CD46 revealed that a minimum length of four CCPs is essential for receptor function. An increase of the distance between the virus binding domain and the plasma membrane by insertion of one to six CCPs of bovine C4 binding protein exhibited only a minor influence on susceptibility to BVDV.The genus Pestivirus comprises bovine viral diarrhea viruses (BVDV type 1 [BVDV-1] and BVDV-2) as well as classical swine fever virus (CSFV) and border disease virus. Pestiviruses are small (40-to 60-nm) enveloped RNA viruses, which together with members of the genera Flavivirus and Hepacivirus constitute the family Flaviviridae (24). The enveloped virion consists of a message-sense single-stranded RNA of about 12,300 nucleotides and four structural proteins, namely, the capsid protein and the three glycoproteins E rns , E1, and E2 (38). The host range of pestiviruses is restricted to clovenhoofed animals (Artiodactyla, e.g., ruminants and pigs) in vivo as well as in cell culture; however, certain cell lines from the rabbit and the domestic cat have been shown to be susceptible to BVDV (4). Within the group of cloven-hoofed animals BVDV is frequently observed to cross species barriers.Recently increasing evidence has enlarged the understanding of the mechanism by which pestiviruses attach to their host cells. Heparan sulfate has been shown to act as a cellular receptor for tissue culture-adapted BVDV and CSFV (16,17). A point mutation resulting in a basic amino acid (Arg 476 ) within the C-terminal domain of the glycoprotein E rns was reported to account for an increased affinity to heparan sulfate (18). We have reported that bovine CD46 acts as a cellular receptor for BVDV (29). BVDV binding to CD46 and an increased susceptibility of bovi...

Although cattle develop humoral immune responses to Shiga-toxigenic (Stx

Airborne pathogens - either transmitted via aerosol or droplets - include a wide variety of highly infectious and dangerous microbes such as variola virus, measles virus, influenza A viruses, Mycobacterium tuberculosis, Streptococcus pneumoniae, and Bordetella pertussis. Emerging zoonotic pathogens, for example, MERS coronavirus, avian influenza viruses, Coxiella, and Francisella, would have pandemic potential were they to acquire efficient human-to-human transmissibility. Here, we synthesize insights from microbiological, medical, social, and economic sciences to provide known mechanisms of aerosolized transmissibility and identify knowledge gaps that limit emergency preparedness plans. In particular, we propose a framework of drivers facilitating human-to-human transmission with the airspace between individuals as an intermediate stage. The model is expected to enhance identification and risk assessment of novel pathogens.

BackgroundThe epidemiological situation of ovine chlamydial infections in continental Europe, especially Germany is poorly characterised. Using the German state of Thuringia as a model example, the chlamydial sero- and antigen prevalence was estimated in thirty-two randomly selected sheep flocks with an average abortion rate lower than 1%. Seven vaccinated flocks were reviewed separately.ResultsA wide range of samples from 32 flocks were examined. Assumption of a seroprevalence of 10% (CI 95%) at flock level, revealed that 94% of the tested flocks were serologically positive with ongoing infection (i.e. animals with seroconversion) in nearly half (47%) of the flocks. On the basis of an estimated 25% antigen prevalence (CI 95%), PCR and DNA microarray testing, together with sequencing revealed the presence of chlamydiae in 78% of the flocks. The species most frequently found was Chlamydophila (C.) abortus (50%) followed by C. pecorum (47%) and C. psittaci genotype A (25%). Mixed infections occurred in 25% of the tested flocks. Samples obtained from the vaccinated flocks revealed the presence of C. abortus field samples in 4/7 flocks. C. pecorum was isolated from 2/7 flocks and the presence of seroconversion was determined in 3/7 flocks.ConclusionsThe results imply that chlamydial infections occur frequently in German sheep flocks, even in the absence of elevated abortion rates. The fact that C. pecorum and the potentially zoonotic C. psittaci were found alongside the classical abortifacient agent C. abortus, raise questions about the significance of this reservoir for animal and human health and underline the necessity for regular monitoring. Further studies are needed to identify the possible role of C. psittaci infections in sheep.