High-resolution crystal structure of FKBP12 from Aedes aegypti

Dengue is one of the most infectious viral diseases prevalent mainly in tropical countries. The virus is transmitted by Aedes species of mosquito, primarily Aedes aegypti. Dengue remains a challenging drug target for years as the virus eludes the immune responses. Currently, no vaccines or antiviral drugs are available for dengue prevention. Previous studies suggested that the immunosuppressive drug FK506 shows antimalarial activity, and its molecular target, FK506‐binding protein (FKBP), was identified in the Plasmodium parasite. Likewise, a FKBP family protein has been identified in A. aegypti (AaFKBP12) in which AaFKBP12 is assumed to play a similar role in its life cycle. FKBPs belong to a highly conserved class of proteins and are considered as an attractive pharmacological target. Herein, we present a high‐resolution crystal structure of AaFKBP12 at 1.3 Å resolution and discuss its structural features throwing light in facilitating the design of potential antagonists against the dengue‐transmitting mosquito.     

Recombinant Newcastle disease virus expressing African swine fever virus protein 72 is safe and immunogenic in mice

African swine fever(ASF) is a lethal hemorrhagic disease that affects wild and domestic swine. The etiological agent of ASF is African swine fever virus(ASFV). Since the first case was described in Kenya in 1921, the disease has spread to many other countries. No commercial vaccines are available to prevent ASF. In this study, we generated a recombinant Newcastle disease virus(r NDV) expressing ASFV protein 72(p72) by reverse genetics and evaluated its humoral and cellular immunogenicity in a mouse model. The recombinant virus, r NDV/p72, replicated well in embryonated chicken eggs and was safe to use in chicks and mice. The p72 gene in r NDV/p72 was stably maintained through ten passages. Mice immunized with r NDV/p72 developed high titers of ASFV p72 specific Ig G antibody, and had higher levels of Ig G1 than IgG2 a. Immunization also elicited T-cell proliferation and secretion of IFN-γ and IL-4. Taken together, these results indicate that r NDV expressing ASFV p72 might be a potential vaccine candidate for preventing ASF.     

The relative contribution of environmental and genetic factors to phenotypic variation in familial Mediterranean fever (FMF)

Introduction

Familial Mediterranean fever (FMF) is an autosomal recessive disease, caused by mutations in the FMF gene MEFV (MEditerranean FeVer). It has a large phenotypic diversity even in patients with similar genotypes. Despite evidence that environmental factors (EFs) and genetic factors, including MEFV mutations (such as M694V, E148Q) and background modifier genes (MGs), affect the clinical manifestations of FMF, the relative contribution of each remains unknown.

Methods

To investigate the relative contribution of environmental and genetic factors to the phenotype of FMF, we compared the intra-pair clinical concordance of 10 mono and 7 dizygotic twins with FMF. The part played by EFs was determined by the phenotypic discordance of the monozygous twins, and the MGs effect was determined by deducing the environmental effect, computed for MZ twins, from the phenotypic discordance of the dizygous twins.

Results

The mean ± SD of intra-pair concordance was higher in the MZ than in DZ twin group (88.1 ± 13.2 vs. 70.7 ± 14.1 respectively, P value < 0.05). Based on the concordance in clinical manifestations in MZ and DZ twins, the environmental effect on the phenotype of FMF is estimated as 11.9% ± 6.6% and the MGs effect as 17.4% ± 15.5% in average.

Conclusions

In FMF the phenotype is affected by MEFV mutations, MGs and EFs in an estimated ratio of about 6:1.5:1 respectively.     

Neglected tropical diseases in Central America and Panama: Review of their prevalence,populations at risk and impact on regional development

A review of the literature since 2009 reveals a staggering health and economic burden resulting from neglected tropical diseases in Panama and the six countries of Central America (referred to collectively here as ‘Central America’). Particularly at risk are the 10.2 million people in the region who live on less than $2 per day, mostly in Guatemala, Honduras, Nicaragua and El Salvador. Indigenous populations are especially vulnerable to neglected tropical diseases. Currently, more than 8 million Central American children require mass drug treatments annually (or more frequently) for their intestinal helminth infections, while vector-borne diseases are widespread. Among the vector-borne parasitic infections, almost 40% of the population is at risk for malaria (mostly Plasmodium vivax infection), more than 800,000 people live with Chagas disease, and up to 39,000 people have cutaneous leishmaniasis. In contrast, an important recent success story is the elimination of onchocerciasis from Central America. Dengue is the leading arbovirus infection with 4–5 million people affected annually and hantavirus is an important rodent-borne viral neglected tropical disease. The leading bacterial neglected tropical diseases include leptospirosis and trachoma, for which there are no disease burden estimates. Overall there is an extreme dearth of epidemiological data on neglected tropical diseases based on active surveillance as well as estimates of their economic impact. Limited information to date, however, suggests that neglected tropical diseases are a major hindrance to the region’s economic development, in both the most impoverished Central American countries listed above, as well as for Panama and Costa Rica where a substantial (but largely hidden) minority of people live in extreme poverty.     

Hyalomma ticks on northward migrating birds in southern Spain: Implications for the risk of entry of Crimean‐Congo haemorrhagic fever virus to Great Britain

Crimean‐Congo haemorrhagic fever virus (CCHFV) is a zoonotic virus transmitted by Hyalomma ticks, the immature stages of which may be carried by migratory birds. In this study, a total of 12 Hyalomma ticks were recovered from five of 228 migratory birds trapped in Spring, 2012 in southern Spain along the East Atlantic flyway. All collected ticks tested negative for CCHFV. While most birds had zero Hyalomma ticks, two individuals had four and five ticks each and the statistical distribution of Hyalomma tick counts per bird is over‐dispersed compared to the Poisson distribution, demonstrating the need for intensive sampling studies to avoid underestimating the total number of ticks. Rates of tick exchange on migratory birds during their northwards migration will affect the probability that a Hyalomma tick entering Great Britain is positive for CCHFV. Drawing on published data, evidence is presented that the latitude of a European country affects the probability of entry of Hyalomma ticks on wild birds. Further data on Hyalomma infestation rates and tick exchange rates are required along the East Atlantic flyway to further our understanding of the origin of Hyalomma ticks (i.e., Africa or southern Europe) and hence the probability of entry of CCHFV into GB.     

Maternal influenza during pregnancy and risk of congenital abnormalities in offspring

BACKGROUND: The teratogenic effect of influenza viruses is currently being debated, and we examined the large population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA) to study the possible association between maternal influenza and various congenital abnormalities (CAs). METHODS: The 1980-1996 HCCSCA includes 22,843 newborns or fetuses with CAs, and 38,151 matched controls (newborn infants without any abnormalities). RESULTS: In the case group, 1328 (5.8%) mothers had influenza at some time during their pregnancies compared to 1838 (4.8%) mothers in the control group (adjusted prevalence odds ratios [PORs], 1.3; 95% confidence interval [CI], 1.2-1.4). In the calculation of the adjusted PORs, the use of antifever drugs and maternal employment status were considered. When cases and their matched controls were compared, there was a higher prevalence of maternal influenza during the second and/or third month of pregnancy for the group of newborns with cleft lip +/- palate (adjusted POR, 3.2; 95% CI, 2.0-5.3), neural-tube defects (adjusted POR, 1.9; 95% CI, 1.1-3.3), and cardiovascular malformations (adjusted POR, 1.7; 95% CI, 1.3-2.3). However, a direct teratogenic effect from influenza viruses appears to be unlikely, and we suggest that the higher prevalence of the CAs indicated above can be explained mainly by fever, because this risk was reduced by the use of antifever drugs. Periconceptional folic acid supplementation also showed some preventive effect for these CAs. CONCLUSIONS: The indirect teratogenic effect of maternal influenza during pregnancy may be restricted by appropriate medical treatment (e.g., antifever drugs) and periconceptional folic acid supplementation.     

原位分子杂交法检测恙螨体内肾综合征出血热病毒核酸的研究

为探讨肾综合征出血热病毒（ＨＦＲＳＶ）在恙螨体内的分布和定位,采用原位分子杂交技术检测恙螨体内ＨＦＲＳＶＲＮＡ。结果发现：原位分子杂交技术的检出阳性率较ＩＦＡＴ高;ＨＦＲＳＶ阳性信号颗粒呈弥散分布,多见于恙螨幼虫和若虫的腹部组织细胞内,该部位是恙螨的卵巢细胞、中肠及支囊上皮细胞。前体组织细胞内少见;个别幼虫和若虫的前足和中足细胞内亦可见到ＨＦＲＳＶＲＮＡ阳性信号。在原位分子杂交中,若虫组织细胞内的ＨＦＲＳＶＲＮＡ阳性信号较幼虫密集而且量多,表明ＨＦＲＳＶ在恙螨体内可传递并有增殖现象     

A randomised double-blind clinical trial of two yellow fever vaccines prepared with substrains 17DD and 17D-213/77 in children nine-23 months old

This randomised, double-blind, multicentre study with children nine-23 months oldevaluated the immunogenicity of yellow fever (YF) vaccines prepared with substrains17DD and 17D-213/77. YF antibodies were tittered before and 30 or more days aftervaccination. Seropositivity and seroconversion were analysed according to thematernal serological status and the collaborating centre. A total of 1,966 childrenwere randomised in the municipalities of the states of Mato Grosso do Sul, MinasGerais and São Paulo and blood samples were collected from 1,714 mothers.Seropositivity was observed in 78.6% of mothers and 8.9% of children beforevaccination. After vaccination, seropositivity rates of 81.9% and 83.2%,seroconversion rates of 84.8% and 85.8% and rates of a four-fold increase over thepre-vaccination titre of 77.6% and 81.8% were observed in the 17D-213/77 and 17DDsubgroups, respectively. There was no association with maternal immunity. Amongchildren aged 12 months or older, the seroconversion rates of 69% were associatedwith concomitant vaccination against measles, mumps and rubella. The data were notconclusive regarding the interference of maternal immunity in the immune response tothe YF vaccine, but they suggest interference from other vaccines. Thefailures in seroconversion after vaccination support therecommendation of a booster dose in children within 10 years of the first dose.