Meningococcal disease occurs worldwide with incidence rates varying from 1 to 1000 cases per 100,000. The causative organism, Neisseria meningitidis, is an obligate commensal of humans, which normally colonizes the mucosa of the upper respiratory tract without causing invasive disease, a phenomenon known as carriage. Studies using molecular methods have demonstrated the extensive genetic diversity of meningocococci isolated from carriers, in contrast to a limited number of genetic types, known as the hyperinvasive lineages, associated with invasive disease. Population and evolutionary models that invoke positive selection can be used to resolve the apparent paradox of virulent lineages persisting during the global spread of a non-clonal and normally commensal bacterium. The application of insights gained from studies of meningococcal population biology and evolution is important in understanding the spread of disease, as well as in vaccine development and implementation, especially with regard to the challenge of producing comprehensive vaccines based on sub-capsular antigens and measuring their effectiveness.
Noroviruses, belonging to the family Caliciviridae, have been identified in human beings and in several animal species including cattle. The distribution of bovine norovirus infections was investigated by both RT-PCR to detect norovirus genomes and a virus-like particles-based ELISA to detect genotype 2 bovine norovirus antibodies. During a 1-year systematic study, a virus prevalence of 7.5% (CI 95%: [3.7; 13.4%]) (10 out of 133 samples) was found in stool samples from diarrhoeic calves screened by RT-PCR. Nucleotide sequencing performed on the polymerase region classified all the norovirus amplicons in the bovine norovirus genotype 2. Rather surprisingly, some rotavirus sequences were also detected. On the basis of the polymerase region, genotype 1 bovine norovirus was not identified. Other enteropathogens were found in all samples. By ELISA, a genotype 2 seroprevalence of 93.2% (CI 95%: [90.4; 95.3%]) was found from calves and adult cattle. Antibody levels against genotype 2 bovine noroviruses rose in the first 6 months of life and were maintained in adults. Together the results of virus prevalence and seroprevalence studies suggest that bovine norovirus infection occurs early in life and that re-infection with serologically related bovine noroviruses strains could occur in adult cattle as reported for rotaviruses. The antibody rise against genotype 2 bovine noroviruses in the adult cattle also suggests a short lived and/or strain specific immunity as already shown in human noroviruses. Genotype 2 bovine noroviruses are endemic in the region investigated.
Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) is an important binding receptor for dengue virus (DENV) that recognizes N-glycosylation sites on the viral E-glycoprotein. DENV cannot bind nor infect the human B-cell line Raji/0. However, DENV productively infects Raji/DC-SIGN(+) cells that constitutively express DC-SIGN on their surface. IL-4-treated monocytes, expressing high levels of DC-SIGN, are also susceptible for DENV infection. Several carbohydrate-binding agents (CBAs), such as the plant lectins HHA, GNA (mannose-specific) and UDA (N-acetylglucosamine-specific), inhibited dose-dependently the binding of DENV and subsequently viral replication in Raji/DC-SIGN(+) cells (EC(50): 0.1-2.2 microM). These CBAs were clearly more active against DENV in IL-4-treated monocytes (EC(50): 4-56 nM). However, the CBAs were devoid of antiviral activity in DENV-susceptible Vero-B (DC-SIGN(-)) cells, demonstrating cell type-dependent differences in viral entry mechanisms.
Human cytomegalovirus (HCMV) lytic DNA replication is initiated at the cis-acting oriLyt region and requires six core replication proteins along with UL84 and IE2. Although UL84 is thought to be the replication initiator protein, little is known about its interaction with oriLyt. We have now performed chromatin immunoprecipitation assays (ChIP) using antibodies specific to UL84, IE2, UL44, CCAAT/enhancer binding protein (C/EBPalpha) and PCR primers that span the entire oriLyt region to reveal an evaluation of specific protein binding across oriLyt. UL84 interacted with several regions of oriLyt that contain C/EBPalpha transcription factor binding sites. Mutation of either of one of C/EBPalpha (92,526 or 92,535) sites inactivated oriLyt and resulted in the loss of binding of UL84. These data reveal the regions of interaction within oriLyt for several key replication proteins and show that the interaction between UL84 and C/EBPalpha sites within oriLyt is essential for lytic DNA replication.
We have reported that human respiratory coronavirus OC43 (HCoV-OC43) is neurotropic and neuroinvasive in humans and mice, and that neurons are the primary target of infection in mice, leading to neurodegenerative disabilities. We now report that an HCoV-OC43 mutant harboring two persistence-associated S glycoprotein point mutations (H183R and Y241H), induced a stronger unfolded protein response (UPR) and translation attenuation in infected human neurons. There was a major contribution of the IRE1/XBP1 pathway, followed by caspase-3 activation and nuclear fragmentation, with no significant role of the ATF6 and eIF2-alpha/ATF4 pathways. Our results show the importance of discrete molecular viral S determinants in virus-neuronal cell interactions that lead to increased production of viral proteins and infectious particles, enhanced UPR activation, and increased cytotoxicity and cell death. As this mutant virus is more neurovirulent in mice, our results also suggest that two mutations in the S glycoprotein could eventually modulate viral neuropathogenesis.
The relative contributions of stimulus salience and task-related goals in guiding attention remain an issue of debate. Several studies have demonstrated that top-down factors play an important role, as they often override capture by salient irrelevant objects. However, Yantis and Egeth [Yantis, S., & Egeth, H. E. (1999). On the distinction between visual salience and stimulus-driven attentional capture. Journal of Experimental Psychology: Human Perception and Performance, 25, 661-676.] have made the more radical claim that salience plays no role in visual search unless the observer adopts an attentional set for singletons or "singleton-detection mode". We reexamine their claim while disentangling effects of stimulus salience from effects of attentional set and inter-trial repetition. The results show that stimulus salience guides attention even when salience is task irrelevant.
Strong and sustained HPV-16 and -18 antibody responses have been observed in previously unexposed women aged 15-25 years vaccinated with the AS04-adjuvanted HPV-16/18 L1 virus-like particle vaccine. While awaiting the extended results of ongoing trials, our objective was to predict the long-term persistence of anti-HPV-16/18 antibodies in vaccinees by applying three statistical models using immunogenicity data from vaccinated women with serum samples collected up to 6.4 years after first vaccination. Two different data lock-points (up to 5.5 years and up to 6.4 years) were used to assess the robustness of the models.