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The interaction of viral surface components with cellular receptors and other entry factors determines key features of viral infection such as host range, tropism and virulence. Despite intensive research, our understanding of these interactions remains limited. Here, we report a systematic analysis of published work on mammalian virus receptors and attachment factors. We build a dataset twice the size of those available to date and specify the role of each factor in virus entry. We identify cellular proteins that are preferentially used as virus receptors, which tend to be plasma membrane proteins with a high propensity to interact with other proteins. Using machine learning, we assign cell surface proteins a score that predicts their ability to function as virus receptors. Our results also reveal common patterns of receptor usage among viruses and suggest that enveloped viruses tend to use a broader repertoire of alternative receptors than non-enveloped viruses, a feature that might confer them with higher interspecies transmissibility.

We report the genome of the facultative intracellular parasite Rhodococcus equi, the only animal pathogen within the biotechnologically important actinobacterial genus Rhodococcus. The 5.0-Mb R. equi 103S genome is significantly smaller than those of environmental rhodococci. This is due to genome expansion in nonpathogenic species, via a linear gain of paralogous genes and an accelerated genetic flux, rather than reductive evolution in R. equi. The 103S genome lacks the extensive catabolic and secondary metabolic complement of environmental rhodococci, and it displays unique adaptations for host colonization and competition in the short-chain fatty acid-rich intestine and manure of herbivores two main R. equi reservoirs. Except for a few horizontally acquired (HGT) pathogenicity loci, including a cytoadhesive pilus determinant (rpl) and the virulence plasmid vap pathogenicity island (PAI) required for intramacrophage survival, most of the potential virulence-associated genes identified in R. equi are conserved in environmental rhodococci or have homologs in nonpathogenic Actinobacteria. This suggests a mechanism of virulence evolution based on the cooption of existing core actinobacterial traits, triggered by key host niche-adaptive HGT events. We tested this hypothesis by investigating R. equi virulence plasmid-chromosome crosstalk, by global transcription profiling and expression network analysis. Two chromosomal genes conserved in environmental rhodococci, encoding putative chorismate mutase and anthranilate synthase enzymes involved in aromatic amino acid biosynthesis, were strongly coregulated with vap PAI virulence genes and required for optimal proliferation in macrophages. The regulatory integration of chromosomal metabolic genes under the control of the HGT-acquired plasmid PAI is thus an important element in the cooptive virulence of R. equi.

Current diagnostic methods for detection of Streptococcus pneumoniae in children with suspected invasive pneumococcal disease have limitations of accuracy, timeliness, and patient convenience. This study aimed to determine the performance of pneumococcal load quantified with a real-time polymerase-chain reaction in nasopharyngeal samples to diagnose invasive pneumococcal disease in children. Matched case-control study of patients <5 years of age with invasive pneumococcal disease admitted to the Manhiça District Hospital (Mozambique) and asymptomatic controls recruited in different periods between 2006 and 2014. Cases were confirmed by a positive bacterial culture for S. pneumoniae in blood or cerebrospinal fluid. Nasopharyngeal aspirates were collected from cases and controls and pneumococcal density was quantified by lytA real-time polymerase-chain reaction. Thirty cases (median age 12.8 months) and sixty controls (median age 11.7 months) were enrolled and 70% of them were male. Nasopharyngeal pneumococcal carriage was high in both groups: 28/30 (93.3%) for cases vs. 53/60 (88.3%) for controls (p = 0.71). Mean nasopharyngeal pneumococcal load was identified as a marker for invasive pneumococcal disease (7.0 log10 copies/mL in cases vs. 5.8 log10 copies/mL in controls, p<0.001) and showed good discriminatory power (AUC-ROC: 82.1%, 95% CI 72.5%-91.8%). A colonization density of 6.5 log10 copies/mL was determined as the optimal cut-off value to distinguish cases from controls (sensitivity 75.0%, specificity 73.6%). Use of non-invasive nasopharyngeal aspirates coupled with rapid and accurate quantification of pneumococcal load by real-time polymerase chain reaction has the potential to become a useful surrogate marker for early diagnosis of invasive pneumococcal disease in children.

The transmission of viruses between different host species is a major source of emerging diseases and is of particular concern in the case of zoonotic transmission from mammals to humans. Several zoonosis risk factors have been identified, but it is currently unclear which viral traits primarily determine this process as previous work has focused on a few hundred viruses that are not representative of actual viral diversity. Here, we investigate fundamental virological traits that influence cross-species transmissibility and zoonotic propensity by interrogating a database of over 12,000 mammalian virus–host associations. Our analysis reveals that enveloped viruses tend to infect more host species and are more likely to be zoonotic than nonenveloped viruses, while other viral traits such as genome composition, structure, size, or the viral replication compartment play a less obvious role. This contrasts with the previous notion that viral envelopes did not significantly impact or even reduce zoonotic risk and should help better prioritize outbreak prevention efforts. We suggest several mechanisms by which viral envelopes could promote cross-species transmissibility, including structural flexibility of receptor-binding proteins and evasion of viral entry barriers.

The interaction of viral surface components with cellular receptors and other entry factors determines key features of viral infection such as host range, tropism and virulence. Despite intensive research, our understanding of these interactions remains limited. Here, we report a systematic analysis of published work on mammalian virus receptors and attachment factors. We build a dataset twice the size of those available to date and specify the role of each factor in virus entry. We identify cellular proteins that are preferentially used as virus receptors, which tend to be plasma membrane proteins with a high propensity to interact with other proteins. Using machine learning, we assign cell surface proteins a score that predicts their ability to function as virus receptors. Our results also reveal common patterns of receptor usage among viruses and suggest that enveloped viruses tend to use a broader repertoire of alternative receptors than non-enveloped viruses, a feature that might confer them with higher interspecies transmissibility.

Obesity is associated with increased health risk and has been associated with alterations in bacterial gut microbiota, with mainly a reduction in Bacteroidetes, but few data exist at the genus and species level. It has been reported that the Lactobacillus and Bifidobacterium genus representatives may have a critical role in weight regulation as an anti-obesity effect in experimental models and humans, or as a growth-promoter effect in agriculture depending on the strains. To confirm reported gut alterations and test whether Lactobacillus or Bifidobacterium species found in the human gut are associated with obesity or lean status, we analyzed the stools of 68 obese and 47 controls targeting Firmicutes, Bacteroidetes, Methanobrevibacter smithii, Lactococcus lactis, Bifidobacterium animalis and seven species of Lactobacillus by quantitative PCR (qPCR) and culture on a Lactobacillus-selective medium. In qPCR, B. animalis (odds ratio (OR)=0.63; 95% confidence interval (CI) 0.39-1.01; P=0.056) and M. smithii (OR=0.76; 95% CI 0.59-0.97; P=0.03) were associated with normal weight whereas Lactobacillus reuteri (OR=1.79; 95% CI 1.03-3.10; P=0.04) was associated with obesity. The gut microbiota associated with human obesity is depleted in M. smithii. Some Bifidobacterium or Lactobacillus species were associated with normal weight (B. animalis) while others (L. reuteri) were associated with obesity. Therefore, gut microbiota composition at the species level is related to body weight and obesity, which might be of relevance for further studies and the management of obesity. These results must be considered cautiously because it is the first study to date that links specific species of Lactobacillus with obesity in humans.

Cross-species transmission of animal viruses poses a threat to human health. However, systematic experimental assessments of these risks remain scarce. A critical step in viral infection is cellular internalization mediated by viral receptor-binding proteins (RBPs). Here we constructed viral pseudotypes bearing the RBPs of 102 enveloped RNA viruses and assayed their infectivity across 5,202 RBP-cell combinations. This showed that most of the tested viruses have the potential to enter human cells. Pseudotype infectivity varied widely among the 14 viral families examined and was influenced by RBP characteristics, host of origin and target cell type. Cellular gene expression data revealed that the availability of specific cell-surface receptors is not necessarily the main factor limiting viral entry and that additional host factors must be considered. Altogether, these results suggest weak interspecies barriers in the early stages of infection and advance our understanding of the molecular interactions driving viral zoonosis.

Background Current diagnostic methods for detection of Streptococcus pneumoniae in children with suspected invasive pneumococcal disease have limitations of accuracy, timeliness, and patient convenience. This study aimed to determine the performance of pneumococcal load quantified with a real-time polymerase-chain reaction in nasopharyngeal samples to diagnose invasive pneumococcal disease in children. Methods Matched case-control study of patients <5 years of age with invasive pneumococcal disease admitted to the Manhiça District Hospital (Mozambique) and asymptomatic controls recruited in different periods between 2006 and 2014. Cases were confirmed by a positive bacterial culture for S. pneumoniae in blood or cerebrospinal fluid. Nasopharyngeal aspirates were collected from cases and controls and pneumococcal density was quantified by lytA real-time polymerase-chain reaction. Results Thirty cases (median age 12.8 months) and sixty controls (median age 11.7 months) were enrolled and 70% of them were male. Nasopharyngeal pneumococcal carriage was high in both groups: 28/30 (93.3%) for cases vs. 53/60 (88.3%) for controls (p = 0.71). Mean nasopharyngeal pneumococcal load was identified as a marker for invasive pneumococcal disease (7.0 log10 copies/mL in cases vs. 5.8 log10 copies/mL in controls, p<0.001) and showed good discriminatory power (AUC-ROC: 82.1%, 95% CI 72.5%-91.8%). A colonization density of 6.5 log10 copies/mL was determined as the optimal cut-off value to distinguish cases from controls (sensitivity 75.0%, specificity 73.6%). Conclusion Use of non-invasive nasopharyngeal aspirates coupled with rapid and accurate quantification of pneumococcal load by real-time polymerase chain reaction has the potential to become a useful surrogate marker for early diagnosis of invasive pneumococcal disease in childre

Purpose Many epidemiological studies find an inverse correlation between carotenoids intake or carotenoids plasma concentrations and body mass index (BMI), insulin resistance or metabolic syndrome in the general population. However, it is not clear whether these relationships occur in obese population. Methods We conducted a cross-sectional study in 108 obese non-diabetic patients. Results There was an inverse correlation between plasma levels of pro-vitamin A carotenoids (α-carotene, β-carotene and β-cryptoxanthin) and both BMI and insulin resistance (estimated by the HOMA-IR). No correlation between plasma concentrations of lycopene or lutein/zeaxanthin and BMI or insulin resistance was found. The inverse association between the three pro-vitamin A carotenoids and HOMA-IR disappeared after adjustment for BMI and waist circumference. Interestingly, we identified a positive association between concentrations of β-carotene and adiponectin in plasma that was independent of sex, age, smoking status, BMI and waist circumference. To our knowledge, such association has never been described in obese patients. Conclusion These results suggest the existence of a favourable effect of β-carotene on insulin sensitivity in obese individuals that could involve a positive regulation of adiponectin, either directly or via its pro-vitamin A activity. The demonstration of the potential benefits of β-carotene towards insulin sensitivity would open the way to dietary strategies to prevent metabolic syndrome.

Background: No recognized risk factors can be identified in 10-40% of hepatitis C virus (HCV)-infected patients suggesting that the modes of transmission involved could be underestimated or unidentified. Invasive diagnostic procedures, such as endoscopy, have been considered as a potential HCV transmission route; although the actual extent of transmission in endoscopy procedures remains controversial. Most reported HCV outbreaks related to nosocomial acquisition have been attributed to unsafe injection practices and use of multi-dose vials. Only a few cases of likely patient-to-patient HCV transmission via a contaminated colonoscope have been reported to date. Nosocomial HCV infection may have important medical and legal implications and, therefore, possible transmission routes should be investigated. In this study, a case of nosocomial transmission of HCV from a common source to two patients who underwent colonoscopy in an endoscopy unit is reported. Results: A retrospective epidemiological search after detection of index cases revealed several potentially infective procedures: sample blood collection, use of a peripheral catheter, anesthesia and colonoscopy procedures. The epidemiological investigation showed breaches in colonoscope reprocessing and deficiencies in the recording of valuable tracing data. Direct sequences from the NS5B region were obtained to determine the extent of the outbreak and cloned sequences from the E1-E2 region were used to establish the relationships among intrapatient viral populations. Phylogenetic analyses of individual sequences from viral populations infecting the three patients involved in the outbreak confirmed the patient pointed out by the epidemiological search as the source of the outbreak. Furthermore, the sequential order in which the patients underwent colonoscopy correlates with viral genetic variability estimates. Conclusions: Patient-to-patient transmission of HCV could be demonstrated although the precise route of transmission remained unclear. Viral genetic variability is proposed as a useful tool for tracing HCV transmission, especially in recent transmissions.