Bat ASC2 suppresses inflammasomes and ameliorates inflammatory diseases.

Bats are special in their ability to live long and host many emerging viruses. Our previous studies showed that bats have altered inflammasomes, which are central players in aging and infection. However, the role of inflammasome signaling in combating inflammatory diseases remains poorly understood. Here, we report bat ASC2 as a potent negative regulator of inflammasomes. Bat ASC2 is highly expressed at both the mRNA and protein levels and is highly potent in inhibiting human and mouse inflammasomes. Transgenic expression of bat ASC2 in mice reduced the severity of peritonitis induced by gout crystals and ASC particles. Bat ASC2 also dampened inflammation induced by multiple viruses and reduced mortality of influenza A virus infection. Importantly, it also suppressed SARS-CoV-2-immune-complex-induced inflammasome activation. Four key residues were identified for the gain of function of bat ASC2. Our results demonstrate that bat ASC2 is an important negative regulator of inflammasomes with therapeutic potential in inflammatory diseases.

Retarded decline of the share of SARS-CoV-2-positive children in North Rhine-Westphalia, Germany.

Knowledge on the mechanisms of viral spread, of time-related changes, and age-specific factors of severe acute respiratory syndrome coronavirus 2 infections is important to develop recommendations aimed at controlling the pandemic. In this context, longitudinal data on proportions of positive results in different age groups are rare. Data on total positive counts and on shares of positive counts deriving from a private (MVZ) and a University (RWTH) laboratory were analyzed retrospectively and compared with public data on total positive counts of the Robert Koch Institute (RKI). Data were covered for Weeks 9-24 of the year 2020 and all patient ages. Total positive counts were lower in children compared to adults. Proportions of children and adults tested positive were 3%-5% and 5%-7%, respectively. RKI and MVZ data showed similar time-related patterns. Patients of 20-60 years of age did account for the initial virus spread (maximum infection rates at Weeks 9-11). Thereafter, infection rates decreased in older patients whereas children did not show a comparable time-related decrease. Pediatric data generated in outpatient settings and hospitals differed markedly which should be considered in further studies. In summary, compared with adults children are less affected by severe acute respiratory syndrome coronavirus 2 infections and are unlikely to account for the initial viral spread. However, children show sustained viral activity and may serve as a viral reservoir.

Ultrasensitive detection and quantification of viral nucleic acids with Raindance droplet digital PCR (ddPCR).

Sensitive detection of viral nucleic acids is critically important for diagnosis and monitoring of the progression of infectious diseases such as those caused by SARS-CoV2, HIV-1, and other viruses. In HIV-1 infection cases, assessing the efficacy of treatment interventions that are superimposed on combination antiretroviral therapy (cART) has benefited tremendously from the development of sensitive HIV-1 DNA and RNA quantitation assays. Simian immunodeficiency virus (SIV) infection of Rhesus macaques is similar in many key aspects to human HIV-1 infection and consequently this non-human primate (NHP) model has and continues to prove instrumental in evaluating HIV prevention, treatment and eradication approaches. Cell and tissue associated HIV-1 viral nucleic acids have been found to serve as useful predictors of disease outcome and indicators of treatment efficacy, highlighting the value of and the need for sensitive detection of viruses in cells/tissues from infected individuals or animal models. However, viral nucleic acid detection and quantitation in such sample sources can often be complicated by high nucleic acid input (that is required to detect ultralow level viruses in, for example, cure research) or inhibitors, leading to reduced detection sensitivity and under-quantification, and confounded result interpretation. Here, we present a step-by-step procedure to quantitatively recover cell/tissue associated viral DNA and RNA, using SIV-infected Rhesus macaque cells and tissues as model systems, and subsequently quantify the viral DNA and RNA with an ultrasensitive SIV droplet digital PCR (ddPCR) assay and reverse transcription ddPCR (RT-ddPCR) assay, respectively, on the Raindance ddPCR platform. The procedure can be readily adapted for a broad range of applications where highly sensitive nucleic acid detection and quantitation are required.