Bunyavirus SFTSV NSs utilizes autophagy to escape the antiviral innate immune response.

Severe fever with thrombocytopenia syndrome virus (SFTSV) nonstructural protein (NSs) is an important viral virulence factor that sequesters multiple antiviral proteins into inclusion bodies to escape the antiviral innate immune response. However, the mechanism of the NSs restricting host innate immunity remains largely elusive. Here, we found that the NSs induced complete macroautophagy/autophagy by interacting with the CCD domain of BECN1, thereby promoting the formation of a BECN1-dependent autophagy initiation complex. Importantly, our data showed that the NSs sequestered antiviral proteins such as TBK1 into autophagic vesicles, and therefore promoted the degradation of TBK1 and other antiviral proteins. In addition, the 8A mutant of NSs reduced the induction of BECN1-dependent autophagy flux and degradation of antiviral immune proteins. In conclusion, our results indicated that SFTSV NSs sequesters antiviral proteins into autophagic vesicles for degradation and to escape antiviral immune responses.

SFTSV infection in rodents and their ectoparasitic chiggers.

SFTSV, a tick-borne bunyavirus causing a severe hemorrhagic fever termed as severe fever with thrombocytopenia syndrome (SFTS). To evaluate the potential role of rodents and its ectoparasitic chiggers in the transmission of SFTSV, we collected wild rodents and chiggers on their bodies from a rural area in Qingdao City, Shandong Province, China in September 2020. PCR amplification of the M and L segments of SFTSV showed that 32.3% (10/31) of rodents and 0.2% (1/564) of chiggers (Leptotrombidium deliense) from the rodents were positive to SFTSV. Our results suggested that rodents and chiggers may play an important role in the transmission of SFTSV, although the efficiency of chiggers to transmit SFTSV needs to be further investigated experimentally.

MERS-related CoVs in hedgehogs from Hubei Province, China.

The emerging coronavirus diseases such as COVID-19, MERS, and SARS indicated that animal coronaviruses (CoVs) spillover to humans are a huge threat to public health. Therefore, we needed to understand the CoVs carried by various animals. Wild hedgehogs were collected from rural areas in Wuhan and Xianning cities in Hubei Province for analysis of CoVs. PCR results showed that 5 out of 51 (9.8%) hedgehogs (Erinaceus amurensis) were positive to CoVs in Hubei Province with 3 samples from Wuhan City and 2 samples from Xianning City. Phylogenetic analysis based on the partial sequence of RNA-dependent RNA polymerase showed that the CoVs from hedgehogs are classified into Merbecovirus of the genus Betacoronavirus; the hedgehog CoVs formed a phylogenetic sister cluster with human MERS-CoVs and bat MERS-related CoVs. Among the 12 most critical residues of receptor binding domain in MERS-CoV for binding human Dipeptidyl peptidase 4, 3 residuals were conserved between the hedgehog MERS-related CoV obtained in this study and the human MERS-CoV. We concluded that hedgehogs from Hubei Province carried MERS-related CoVs, indicating that hedgehogs might be important in the evolution and transmission of MERS-CoVs, and continuous surveillance of CoVs in hedgehogs was important.

Cognitive impairment in mice over-expressing gamma-aminobutyric acid transporter 1 (GAT1).

There is increasing evidence that GABAergic system plays an important role in the neural control of learning and memory processes. GAT1 over-expressing mice (NA) were generated, in which GAT1 is under the control of a neuron-specific enolase (NSE) promoter, to investigate effects of GABA transporter on cognitive function. Our results revealed that NA mice displayed cognitive deterioration in associative learning ability and new object recognition retention, compared with the wild-type littermates (WT2). However, the impaired cognitive function of transgenic mice could be rescued after chronic administration of GAT1 selective inhibitor for 6 days. In addition, there was no change of the expression of NMDA receptors in NA mice. Taken together, we show a potentially important role for GAT1 in the neural control of cognitive processes, and indicate great potential for GAT1 as a clinical target of cognitive disorders.

Hyperalgesic effects of gamma-aminobutyric acid transporter I in mice.

The present study focused on the involvement of gamma-aminobutyric acid transporter I (GAT1) in pain. We found that GABA uptake was increased in mouse spinal cord at 20 min and 120 min after formalin injection and in mouse brain at 120 min, but not 20 min, after formalin injection. In addition, the antinociceptive effects of GAT1-selective inhibitors were examined using assays of thermal (tail-flick) and chemical (formalin and acetic acid) nociception in C57BL/6J mice. The GAT1-selective inhibitors, ethyl nipecotate and NO-711, exhibited significant antinociceptive effects in these nociceptive assays. To study further the effects of GAT1 on pain, we used two kinds of GAT1-overexpressing transgenic mice (under the control of a CMV promoter or a NSE promoter) to examine the nociceptive responses in these mice. In the thermal, formalin, and acetic acid assays, both kinds of transgenic mice displayed significant hyperalgesia after nociceptive stimuli. In addition, the micro opioid receptor antagonist naloxone had no influence on nociceptive responses in wild-type and transgenic mice. The results indicate that GAT1 is involved in the regulation of pain processes, and point to the possibility of developing analgesic drugs that target GAT1 other than opioid receptors.