Distinct microbiome profiles and biofilms in Leishmania donovani-driven cutaneous leishmaniasis wounds

The endemic strain of Leishmania donovani in Sri Lanka causes cutaneous leishmaniasis (CL) rather than more common visceral form. We have visualized biofilms and profiled the microbiome of lesions and unaffected skin in thirty-nine CL patients. Twenty-four lesions (61.5%) were biofilm-positive according to fluorescence in situ hybridization. Biopsies of biofilm-positive lesions were dominated by Pseudomonas, class Bacilli and Enterobacteriaceae and distinguished by significantly lower community evenness. Higher relative abundance of a class Bacilli OTU was detected in wound swabs versus contralateral skin. Wound swabs and biopsies had significantly distinct microbiome profiles and lower diversity compared to unaffected skin. Greater abundances of potentially pathogenic organisms were observed in wet ulcers, lesions with high parasite loads and large wounds. In summary, more than half of L. donovani associated CL wounds harboured biofilms and the wounds exhibited a distinct, less diverse, microbiome than unaffected skin.

Molecular Pathogenesis and Immune Evasion of Vesicular Stomatitis New Jersey Virus Inferred from Genes Expression Changes in Infected Porcine Macrophages

The molecular mechanisms associated with the pathogenesis of vesicular stomatitis virus (VSV) in livestock remain poorly understood. Several studies have highlighted the relevant role of macrophages in controlling the systemic dissemination of VSV during infection in different animal models, including mice, cattle, and pigs. To gain more insight into the molecular mechanisms used by VSV to impair the immune response in macrophages, we used microarrays to determine the transcriptomic changes produced by VSV infection in primary cultures of porcine macrophages. The results indicated that VSV infection induced the massive expression of multiple anorexic, pyrogenic, proinflammatory, and immunosuppressive genes. Overall, the interferon (IFN) response appeared to be suppressed, leading to the absence of stimulation of interferon-stimulated genes (ISG). Interestingly, VSV infection promoted the expression of several genes known to downregulate the expression of IFN. This represents an alternate mechanism for VSV control of the IFN response, beyond the recognized mechanisms mediated by the matrix protein. Although there was no significant differential gene expression in macrophages infected with a highly virulent epidemic strain compared to a less virulent endemic strain, the endemic strain consistently induced higher expression of all upregulated cytokines and chemokines. Collectively, this study provides novel insights into VSV molecular pathogenesis and immune evasion that warrant further investigation.

Molecular Pathogenesis and Immune Evasion of Vesicular Stomatitis Virus Inferred from Genes Expression Changes in Infected Porcine Macrophages

Molecular mechanisms associated with the pathogenesis of Vesicular stomatitis virus (VSV) in livestock remain poorly understood. Several studies have highlighted the relevant role of macrophages in controlling the systemic dissemination of VSV during infection in different animal models, including mice, cattle and pigs. To gain more insight on the molecular mechanisms used by VSV to impair the immune response in macrophages, we used microarrays to determine the transcriptomic changes produced by VSV infection in primary cultures of porcine macrophages. The results indicated that VSV infection induced the massive expression of multiple anorexic, pyrogenic, proinflammatory and immunosuppressive genes. Overall, the interferon (IFN) response appeared suppressed, leading to the absence of stimulation of interferon-stimulated genes (ISG). Interestingly, VSV infection promoted the expression of several genes known to downregulate the expression of IFNb. This represents an alternate mechanism for VSV control of the IFN response, beyond the recognized mechanisms mediated by the matrix protein. Although there was no significant differential gene expression in macrophages infected with a highly virulent epidemic strain compared to a less virulent endemic strain, the endemic strain consistently induced higher expression of all upregulated cytokines and chemokines. Collectively, this study provides novel insights into VSV molecular pathogenesis and immune evasion that warrants further investigation

Targeting influenza at the Topologically conserved substructures

H9N2 avian influenza virus is a low pathogenic endemic strain in the domestic poultry of most of the Asian countries. Attempts have extensively failed in eradicating its diverse strains. To find the drug against the evolutionarily conserved substructures, the target protein sequence is analyzed through sequence and modelled structure for mapping the structurally conserved topology. The available drugs are screened against the deciphered topological map through the predicted ADMET and drug-likelihood scores. This study helps to build a theoretical framework to make the foremost potent drug.

Lessons from intensified surveillance of viral hepatitis A, Israel, 2017 and 2018

Introduction Universal vaccination of toddlers has led to very low hepatitis A (HAV) endemicity in Israel. However, sporadic outbreaks still occur, necessitating better surveillance. Aim To implement a comprehensive HAV surveillance programme. Methods In 2017 and 2018, sera from suspected HAV cases that tested positive for anti-HAV IgM antibodies were transferred to the Central Virology Laboratory (CVL) for molecular confirmation and genotyping. Sewage samples were collected in Israel and Palestine* and were molecularly analysed. All molecular (CVL), epidemiological (District Health Offices and Epidemiological Division) and clinical (treating physicians) data were combined and concordantly assessed. Results Overall, 146 cases (78 in 2017 and 68 in 2018, median age 34 years, 102 male) and 240 sewage samples were studied. Most cases (96%) were unvaccinated. In 2017, 89% of cases were male, 45% of whom were men who have sex with men (MSM). In 2018, 49% were male, but only 3% of them were MSM (p < 0.01). In 2017, 82% of cases and 63% of sewage samples were genotype 1A, phylogenetically associated with a global MSM-HAV outbreak. In 2018, 80% of cases and 71% of sewage samples were genotype 1B, related to the endemic strain previously identified in Israel and Palestine*. Environmental analysis revealed clustering of sewage and cases’ sequences, and country-wide circulation of HAV. Conclusions Molecular confirmation of HAV infection in cases and analysis of environmental samples, combined with clinical and epidemiological investigation, may improve HAV surveillance. Sequence-based typing of both clinical and sewage-derived samples could assist in understanding viral circulation.

Targeting influenza at the topologically conserved substructures

ABSTRACTH9N2 avian influenza virus is a low pathogenic endemic strain in the domestic poultry of most of the Asian countries. Attempts have extensively failed in eradicating its diverse strains. To find the drug against the evolutionarily conserved substructures, the target protein sequence is analyzed through sequence and modelled structure for mapping the structurally conserved topology. The available drugs are screened against the deciphered topological map through the predicted ADMET and drug-likelihood scores. This study helps to build a theoretical framework to make the foremost potent drug.

How Bank Vole-PUUV Interactions Influence the Eco-Evolutionary Processes Driving Nephropathia Epidemica Epidemiology—An Experimental and Genomic Approach

In Europe, Puumala virus (PUUV) is responsible for nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS). Despite the presence of its reservoir, the bank vole, on most of French territory, the geographic distribution of NE cases is heterogeneous and NE endemic and non-endemic areas have been reported. In this study we analyzed whether bank vole-PUUV interactions could partly shape these epidemiological differences. We performed crossed-experimental infections using wild bank voles from French endemic (Ardennes) and non-endemic (Loiret) areas and two French PUUV strains isolated from these areas. The serological response and dynamics of PUUV infection were compared between the four cross-infection combinations. Due to logistical constraints, this study was based on a small number of animals. Based on this experimental design, we saw a stronger serological response and presence of PUUV in excretory organs (bladder) in bank voles infected with the PUUV endemic strain. Moreover, the within-host viral diversity in excretory organs seemed to be higher than in other non-excretory organs for the NE endemic cross-infection but not for the NE non-endemic cross-infection. Despite the small number of rodents included, our results showed that genetically different PUUV strains and in a lesser extent their interaction with sympatric bank voles, could affect virus replication and diversity. This could impact PUUV excretion/transmission between rodents and to humans and in turn at least partly shape NE epidemiology in France.

How bank vole-PUUV interactions influence the eco-evolutionary processes driving nephropathia epidemica epidemiology: An experimental and genomic approach

In Europe, Puumala virus (PUUV) is responsible for nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome (HFSR). Despite the presence of its reservoir, the bank vole, on most of French territory, the geographic distribution of NE cases is heterogeneous and NE endemic and non-endemic areas have been reported. In this study we analyzed whether bank vole-PUUV interactions could partly shape these epidemiological differences. We performed crossed-experimental infections using wild bank voles from French endemic (Ardennes) and non-endemic (Loiret) areas, and two French PUUV strains isolated from these areas. The serological response and dynamics of PUUV infection were compared between the four cross-infection combinations. We showed that the serological response and the presence of PUUV in excretory organs were more important in bank voles infected with the PUUV endemic strain. Moreover, the within-host viral diversity in excretory organs was higher than in other non-excretory organs for the NE endemic cross-infection, but not for the NE non-endemic cross-infection. Altogether, our results showed that genetically different PUUV strains, and in a lesser extent their interaction with sympatric bank voles, could affect virus replication and diversity. This could impact PUUV excretion/transmission between rodents and to humans, and in turn at least partly shape NE epidemiology in France.

The monitoring and molecular epizootiology of porcine epidemic diarrhea in Ukraine during 2014-2018

The rapid spread of porcine epidemic diarrhea (PED) in different countries in a short time while and the significant economic damage caused by it were important reasons for conducting long-term monitoring studies in Ukraine. PED monitoring researches conduct carry out during 2014-2018 using RT-PCR and ELISA showed the presence of infection in 14 (66.67%) of 21 examined regions of Ukraine. For the period 2014- 2018, the proportion of PED cases rate was the lowest in 2017 (1.76%) and the highest in 2016 (48.03%). Over the entire period, the percentage seropositive animals progressively decreased to a seronegative status indicator defined in sows in 2018. The results of determination of the virulence of 40 strains of PED virus from different regions of Ukraine using the RT-PCR method proved the circulation of highly virulent strains. The phylogenetic analysis demonstrated that the endemic strain of PED virus is included in the cluster of North American strains and the Chinese strains. Important is the fact that it is not included in the group of European low- virulent S-INDEL strains. Thus, the obtained data indicate a high probability that the PED virus was introduced into Ukraine from the territory of the Asian continent or the United States of America (a high probability that the PED virus was translocated from the territory of the Asian continent or the United States of America into Ukraine).