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The ongoing COVID-19 outbreak has expanded rapidly throughout China. Major behavioral, clinical, and state interventions are underway currently to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, have affected COVID-19 spread in China. We use real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation on transmission in cities across China and ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was well explained by human mobility data. Following the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases are still indicative of local chains of transmission outside Wuhan. This study shows that the drastic control measures implemented in China have substantially mitigated the spread of COVID-19. One sentence summary: The spread of COVID-19 in China was driven by human mobility early on and mitigated substantially by drastic control measures implemented since the end of January.

Viruses have evolved elaborate mechanisms to evade or inactivate the complex system of sensors and signaling molecules that make up the host innate immune response. Here we show that human coronavirus (HCoV) NL63 and severe acute respiratory syndrome (SARS) CoV papain-like proteases (PLP) antagonize innate immune signaling mediated by STING (stimulator of interferon genes, also known as MITA/ERIS/MYPS). STING resides in the endoplasmic reticulum and upon activation, forms dimers which assemble with MAVS, TBK-1 and IKKε, leading to IRF-3 activation and subsequent induction of interferon (IFN). We found that expression of the membrane anchored PLP domain from human HCoV-NL63 (PLP2-TM) or SARS-CoV (PLpro-TM) inhibits STING-mediated activation of IRF-3 nuclear translocation and induction of IRF-3 dependent promoters. Both catalytically active and inactive forms of CoV PLPs co-immunoprecipitated with STING, and viral replicase proteins co-localize with STING in HCoV-NL63-infected cells. Ectopic expression of catalytically active PLP2-TM blocks STING dimer formation and negatively regulates assembly of STING-MAVS-TBK1/IKKε complexes required for activation of IRF-3. STING dimerization was also substantially reduced in cells infected with SARS-CoV. Furthermore, the level of ubiquitinated forms of STING, RIG-I, TBK1 and IRF-3 are reduced in cells expressing wild type or catalytic mutants of PLP2-TM, likely contributing to disruption of signaling required for IFN induction. These results describe a new mechanism used by CoVs in which CoV PLPs negatively regulate antiviral defenses by disrupting the STING-mediated IFN induction.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of the human demyelinating disorder multiple sclerosis (MS). The immune cytokine interferon-gamma (IFN-γ) is believed to participate in disease pathogenesis in both EAE and MS. In the present study, we examined the significance of IFN-γ-oligodendrocyte interactions in the course of EAE. For the purpose of our study, we used the previously described [proteolipid protein/suppressor of cytokine signaling 1 (PLP/SOCS1)] transgenic mouse line that displays suppressed oligodendrocyte responsiveness to IFN-γ.PLP/SOCS1mice developed EAE with an accelerated onset associated with enhanced early inflammation and markedly increased oligodendrocyte apoptosis. Moreover, we found that IFN-γ pretreatment of mature oligodendrocytesin vitrohad a protective effect against oxidative stress and the inhibition of proteasome activity and resulted in upregulation in expression of a number of chemokines, including CXCL10 (IP10), CCL2 (MCP-1), CCL3 (MCP-1α), and CCL5 (RANTES). These results suggest that IFN-γ-oligodendrocyte interactions are of significance to the clinical and pathological aspects of EAE. In addition, the present study suggests that oligodendrocytes are not simply targets of inflammatory injury but active participants of the neuroimmune network operating during the course of EAE.

ObjectivesWe aim to estimate the impact of various mitigation strategies on COVID-19 transmission in a US jail beyond those offered in national guidelines.DesignWe developed a stochastic dynamic transmission model of COVID-19.SettingOne anonymous large urban US jail.ParticipantsSeveral thousand staff and incarcerated individuals.InterventionsThere were four intervention phases during the outbreak: the start of the outbreak, depopulation of the jail, increased proportion of people in single cells and asymptomatic testing. These interventions were implemented incrementally and in concert with one another.Primary and secondary outcome measuresThe basic reproduction ratio, R0, in each phase, as estimated using the next generation method. The fraction of new cases, hospitalisations and deaths averted by these interventions (along with the standard measures of sanitisation, masking and social distancing interventions).ResultsFor the first outbreak phase, the estimated R0 was 8.44 (95% credible interval (CrI): 5.00 to 13.10), and for the subsequent phases, R0,phase 2=3.64 (95% CrI: 2.43 to 5.11), R0,phase 3=1.72 (95% CrI: 1.40 to 2.12) and R0,phase 4=0.58 (95% CrI: 0.43 to 0.75). In total, the jail’s interventions prevented approximately 83% of projected cases, hospitalisations and deaths over 83 days.ConclusionsDepopulation, single celling and asymptomatic testing within jails can be effective strategies to mitigate COVID-19 transmission in addition to standard public health measures. Decision makers should prioritise reductions in the jail population, single celling and testing asymptomatic populations as additional measures to manage COVID-19 within correctional settings.

The COVID-19 pandemic has seen many hurdles to crucial research processes, in particular those that depend on personnel interactions, in providing safeguards against the incipient infectious disease. At the same time, there was a rapid redirection of research, driven by popular and social media and demand for pandemic-related content, to the detriment of non–COVID-19 research and perhaps to COVID-19 research itself. This article provides historical context to research redirection and discusses approaches to optimizing research methodology in the setting of COVID-19 pandemic.

Lycorine potently inhibits flaviviruses in cell culture. At 1.2-microM concentration, lycorine reduced viral titers of West Nile (WNV), dengue, and yellow fever viruses by 10(2)- to 10(4)-fold. However, the compound did not inhibit an alphavirus (Western equine encephalitis virus) or a rhabdovirus (vesicular stomatitis virus), indicating a selective antiviral spectrum. The compound exerts its antiviral activity mainly through suppression of viral RNA replication. A Val-->Met substitution at the 9th amino acid position of the viral 2K peptide (spanning the endoplasmic reticulum membrane between NS4A and NS4B proteins) confers WNV resistance to lycorine, through enhancement of viral RNA replication. Initial chemistry synthesis demonstrated that modifications of the two hydroxyl groups of lycorine can increase the compound's potency, while reducing its cytotoxicity. Taken together, the results have established lycorine as a flavivirus inhibitor for antiviral development. The lycorine-resistance results demonstrate a direct role of the 2K peptide in flavivirus RNA synthesis.

A canine influenza A(H3N2) virus emerged in the United States in February–March 2015, causing respiratory disease in dogs. The virus had previously been circulating among dogs in Asia, where it originated through the transfer of an avian-origin influenza virus around 2005 and continues to circulate. Sequence analysis suggests the US outbreak was initiated by a single introduction, in Chicago, of an H3N2 canine influenza virus circulating among dogs in South Korea in 2015. Despite local control measures, the virus has continued circulating among dogs in and around Chicago and has spread to several other areas of the country, particularly Georgia and North Carolina, although these secondary outbreaks appear to have ended within a few months. Some genetic variation has accumulated among the US viruses, with the appearance of regional-temporal lineages. The potential for interspecies transmission and zoonotic events involving this newly emerged influenza A virus is currently unknown.