Chikungunya virus (CHIKV) is an alphavirus that causes chronic and incapacitating arthralgia in humans. To date, interactions between the immune system and the different stages of the virus life cycle remain poorly defined. We demonstrated for the first time that CHIKV Ags could be detected in vivo in the monocytes of acutely infected patients. Using in vitro experimental systems, whole blood and purified monocytes, we confirmed that monocytes could be infected and virus growth could be sustained. CHIKV interactions with monocytes, and with other blood leukocytes, induced a robust and rapid innate immune response with the production of specific chemokines and cytokines. In particular, high levels of IFN-α were produced rapidly after CHIKV incubation with monocytes. The identification of monocytes during the early phase of CHIKV infection in vivo is significant as infected monocyte/macrophage cells have been detected in the synovial tissues of chronically CHIKV-infected patients, and these cells may behave as the vehicles for virus dissemination. This may explain the persistence of joint symptoms despite the short duration of viremia. Our results provide a better understanding on the basic mechanisms of infection and early antiviral immune responses and will help in the development of future effective control strategies.
Chikungunya virus (CHIKV) is an alphavirus which causes chronic and incapacitating arthralgia in humans. Although previous studies have shown that antibodies against the virus are produced during and after infection, the fine specificity of the antibody response against CHIKV is not known. Here, using plasma from patients at different times postinfection, we characterized the antibody response against various proteins of the virus. We have shown that the E2 and E3 glycoproteins and the capsid and nsP3 proteins are targets of the anti-CHIKV antibody response. Moreover, we have identified the different regions in these proteins which contain the linear epitopes recognized by the anti-CHIKV antibodies and determined their structural localization. Data also illustrated the effect of a single K 252 Q amino acid change at the E2 glycoprotein that was able to influence antibody binding and interaction between the antibodies and epitope because of the changes of epitope-antibody binding capacity. This study provides important knowledge that will not only aid in the understanding of the immune response to CHIKV infection but also provide new knowledge in the design of modern vaccine development. Furthermore, these pathogen-specific epitopes could be used for future seroepidemiological studies that will unravel the molecular mechanisms of human immunity and protection from CHIKV disease.
Chikungunya fever swept across many South and South-east Asian countries, following extensive outbreaks in the Indian Ocean Islands in 2005. However, molecular epidemiological data to explain the recent spread and evolution of Chikungunya virus (CHIKV) in the Asian region are still limited. This study describes the genetic Characteristics and evolutionary relationships of CHIKV strains that emerged in Sri Lanka and Singapore during 2006-2008. The viruses isolated in Singapore also included those imported from the Maldives (n51), India (n52) and Malaysia (n531). All analysed strains belonged to the East, Central and South African (ECSA) lineage and were evolutionarily more related to Indian than to Indian Ocean Islands strains. Unique genetic characteristics revealed five genetically distinct subpopulations of CHIKV in Sri Lanka and Singapore, which were likely to have emerged through multiple, independent introductions. The evolutionary network based on E1 gene sequences indicated the acquisition of an alanine to valine 226 substitution (E1-A226V) by virus strains of the Indian sublineage as a key evolutionary event that contributed to the transmission and spatial distribution of CHIKV in the region. The E1-A226V substitution was found in 95.7 % (133/139) of analysed isolates in 2008, highlighting the widespread establishment of mutated CHIKV strains in Sri Lanka, Singapore and Malaysia. As the E1-A226V substitution is known to enhance the transmissibility of CHIKV by Aedes albopictus mosquitoes, this observation has important implications for the design of vector control strategies to fight the virus in regions at risk of chikungunya fever.
Acquisition of Elizabethkingia infections in intensive care units (ICUs) has risen in the past decade. Treatment of Elizabethkingia infections is challenging due to the lack of effective therapeutic regimens, leading to a high mortality rate. Elizabethkingia infections have long been attributed to Elizabethkingia meningoseptica. Recently, we used whole-genome sequencing to reveal that E. anophelis is the pathogenic agent for an Elizabethkingia outbreak at two ICUs. We performed comparative genomic analysis of seven hospital-isolated E. anophelis strains with five available Elizabethkingia spp. genomes deposited in the National Center for Biotechnology Information Database. A pan-genomic approach was applied to identify the core- and pan-genome for the Elizabethkingia genus. We showed that unlike the hospital-isolated pathogen E. meningoseptica ATCC 12535 strain, the hospital-isolated E. anophelis strains have genome content and organization similar to the E. anophelis Ag1 and R26 strains isolated from the midgut microbiota of the malaria mosquito vector Anopheles gambiae. Both the core- and accessory genomes of Elizabethkingia spp. possess genes conferring antibiotic resistance and virulence. Our study highlights that E. anophelis is an emerging bacterial pathogen for hospital environments.
A new national antimicrobial resistance surveillance program in Singapore public hospitals that uses WHONET detected high levels of methicillin resistance among Staphylococcus aureus (35.3%), carbapenem resistance among Acinetobacter spp. (49.6%), and third-generation cephalosporin resistance among Klebsiella pneumoniae (35.9%) hospital isolates in 2006. Antimicrobial drug resistance is a major problem in Singapore.
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