HTLV-1 Evades Type I Interferon Antiviral Signaling by Inducing the Suppressor of Cytokine Signaling 1 (SOCS1)

Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of Adult T cell Leukemia (ATL) and the neurological disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the majority of HTLV-1–infected individuals remain asymptomatic carriers (AC) during their lifetime, 2–5% will develop either ATL or HAM/TSP, but never both. To better understand the gene expression changes in HTLV-1-associated diseases, we examined the mRNA profiles of CD4+ T cells isolated from 7 ATL, 12 HAM/TSP, 11 AC and 8 non-infected controls. Using genomic approaches followed by bioinformatic analysis, we identified gene expression pattern characteristic of HTLV-1 infected individuals and particular disease states. Of particular interest, the suppressor of cytokine signaling 1—SOCS1—was upregulated in HAM/TSP and AC patients but not in ATL. Moreover, SOCS1 was positively correlated with the expression of HTLV-1 mRNA in HAM/TSP patient samples. In primary PBMCs transfected with a HTLV-1 proviral clone and in HTLV-1-transformed MT-2 cells, HTLV-1 replication correlated with induction of SOCS1 and inhibition of IFN-α/β and IFN-stimulated gene expression. Targeting SOCS1 with siRNA restored type I IFN production and reduced HTLV-1 replication in MT-2 cells. Conversely, exogenous expression of SOCS1 resulted in enhanced HTLV-1 mRNA synthesis. In addition to inhibiting signaling downstream of the IFN receptor, SOCS1 inhibited IFN-β production by targeting IRF3 for ubiquitination and proteasomal degradation. These observations identify a novel SOCS1 driven mechanism of evasion of the type I IFN antiviral response against HTLV-1

Clonal expansion of the macrolide resistant ST386 within pneumococcal serotype 6C in France.

In France, the use of the 7-valent pneumococcal conjugate vaccine (PCV7) lead to an overall significant decrease in PCV7 invasive pneumococcal disease (IPD) incidence. However, the decrease in vaccine serotype prevalence was partially counterbalanced by the serotype replacement phenomenon. In this study, we analyzed the role of the newly described serotype 6C as one of the replacement serotypes. This work was conducted on a large time scale from the early PCV7 era (2002-2003) to the PCV13 era (2010-2011), both on IPD strains recovered from the whole population and nasopharyngeal colonizing strains isolated in infant less than two years, who are known to be the main reservoir for pneumococci. Serotype 6C took advantage over 6A and 6B serotypes, which both decreased over time. A continuous and significant increase in 6C IPD was observed in adults along the study period; in contrast, in children less than two years, only an increase in 6C nasopharyngeal carriage was found, the prevalence of serotype 6C in IPD remaining very low over time. Among 101 6C invasive and colonizing strains studied by MLST, 24 STs were found to be related to three major clonal complexes, CC395, CC176, and CC315. STs related to CC176 tend to disappear after 2009 and were essentially replaced by ST386 (CC315), which dramatically increased over time. This clonal expansion may be explained by the erythromycin and tetracycline resistances associated with this clone. Finally, the decrease observed in nasopharyngeal 6C carriage since 2010, likely related to the PCV13 introduction in the French immunization schedule, is expected to lead to a decrease in 6C IPD in adults thereafter

Sequence-type (ST) distribution of serotype 6C invasive pneumococcal disease (IPD, n = 71) or nasopharyngeal (NP) colonizing (n = 30) strains.

<p>*STs were grouped on the basis of at least five out of seven identical alleles, according to eBURST analysis;</p><p>°According to the Pneumococcal MLST website, <a href="http://spneumoniae.mlst.net" target="_blank">http://spneumoniae.mlst.net</a>; 9 Dec 2013, last accessed;</p>§<p>In bold, major related serotype; in brackets, single report.</p

Prevalence of serotype 6C isolates from 2009 to 2011, in nasopharyngeal (NP) carriage and in invasive pneumococcal disease (IPD) according to age.

<p>*Calculation was performed by the Fisher exact test.</p><p>°Calculation was performed by the Mantel-Haenszel Chi square test.</p><p>NS, Not significant.</p

Antibiotic resistance in carriage and invasive 6B, 6A or 6C pneumococcal isolates over time.

<p>Pen, penicillin; E, erythromycin; T, tetracycline.</p><p>*The main resistance phenotype is indicated in bold.</p

Distribution of serotypes 6A, 6B, and 6C among <i>Streptococcus pneumoniae</i> isolates recovered from invasive pneumococcal disease (meningitis and bacteremia, n = 12,345) according to age group, from 2002 to 2011.

<p>Introduction of PCV7 in France, March 2002, for children at high risk for IPD; Generalization of PCV7 for children <2 years in 2006; Introduction of PCV13 in France, June 2010.</p><p>*Significant trend over the 5 periods, calculation was performed by the extended Mantel-Haenszel Chi square test for linear trend.</p><p>°Serotype conventionally determined as 6A that could not be further tested for serotype 6C.</p><p>NA, Not applicable; NS, not significant.</p

Factors Associated With Severe Nonmeningitis Invasive Pneumococcal Disease in Adults in France

International audienceBackground. In France, pneumococcal vaccination in adults is recommended for risk groups (chronic conditions/immunosuppression). We conducted a study on invasive pneumococcal disease (IPD) in adults to identify factors associated with disease severity and death. Methods. We included IPD cases, excluding meningitis, from 25 acute care hospitals in 6 regions. We defined severe cases as those with shock or severe sepsis or intensive care unit admission/mechanical ventilation. We included deaths occurring within 30 days of hospitalization. Infectious disease specialists collected clinical/microbiological data on cases. Results. During 2014-2017, 908 nonmeningitis IPD cases were diagnosed; 48% were severe, 84% had comorbidities, 21% died. Ninety percent of cases with comorbidities who previously sought health care were not vaccinated against pneumococcus. Compared with previously healthy cases, the risk of severe IPD increased from 20% (adjusted risk ratio [aRR], 1.2; 95% confidence interval [CI], 1.0-1.4) in cases with 1-2 chronic diseases to 30% (aRR, 1.3; 95% CI, 1.0-7.0) in those with >2 chronic diseases. Among risk groups, 13-valent pneumococcal conjugate vaccine (PCV13) serotypes and 23-valent pneumococcal polysaccharide vaccine (PPSV23) nonPCV13 serotypes were more likely to induce severe IPD compared with nonvaccine serotypes (aRR, 1.5; 95% CI, 1.3-1.9; aRR, 1.3; 95% CI, 1.0-1.5, respectively). Conclusions. We observed a cumulative effect of concurrent comorbidities on severe IPD. Vaccine serotypes were more likely to induce severe IPD among risk groups. The missed opportunities for vaccination underscore the need to enhance vaccination in risk groups

Ongoing outbreak of invasive and non-invasive disease due to group A Streptococcus (GAS) type emm66 among homeless and people who inject drugs in England and Wales, January to December 2016

We report an outbreak of invasive and non-invasive disease due to an unusual type of Streptococcus pyogenes(group A Streptococcus, emm66) among a vulnerable, largely homeless population in southern England and Wales, detected in September 2016. Twenty-seven confirmed cases were subsequently identified between 5 January and 29 December 2016; 20 injected drugs and six reported problematic alcohol use. To date, we have ruled out drug-related vehicles of infection and identified few common risk factors