Current insights into human pathogenic phenuiviruses and the host immune system.

Phenuiviruses are a class of segmented negative-sense single-stranded RNA viruses, typically consisting of three RNA segments that encode four distinct proteins. The emergence of pathogenic phenuivirus strains, such as Rift Valley fever phlebovirus (RVFV) in sub-Saharan Africa, Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) in East and Southeast Asia, and Heartland Virus (HRTV) in the United States has presented considerable challenges to global public health in recent years. The innate immune system plays a crucial role as the initial defense mechanism of the host against invading pathogens. In addition to continued research aimed at elucidating the epidemiological characteristics of phenuivirus, significant advancements have been made in investigating its viral virulence factors (glycoprotein, non-structural protein, and nucleoprotein) and potential host-pathogen interactions. Specifically, efforts have focused on understanding mechanisms of viral immune evasion, viral assembly and egress, and host immune networks involving immune cells, programmed cell death, inflammation, nucleic acid receptors, etc. Furthermore, a plethora of technological advancements, including metagenomics, metabolomics, single-cell transcriptomics, proteomics, gene editing, monoclonal antibodies, and vaccines, have been utilized to further our understanding of phenuivirus pathogenesis and host immune responses. Hence, this review aims to provide a comprehensive overview of the current understanding of the mechanisms of host recognition, viral immune evasion, and potential therapeutic approaches during human pathogenic phenuivirus infections focusing particularly on RVFV and SFTSV.

Prevalence and genetic diversity of Anaplasma and Ehrlichia in ticks and domesticated animals in Suizhou County, Hubei Province, China.

Anaplasma and Ehrlichia are tick-borne bacterial pathogens that cause anaplasmoses and ehrlichioses in humans and animals. In this study, we examined the prevalence of Anaplasma and Ehrlichia species in ticks and domesticated animals in Suizhou County, Hubei Province in the central China. We used PCR amplification and DNA sequencing of the 16S rRNA, groEL, and gltA genes to analyze. We collected 1900 ticks, including 1981 Haemaphysalis longicornis and 9 Rhipicephalus microplus, 159 blood samples of goats (n = 152), cattle (n = 4), and dogs (n = 3) from May to August of 2023. PCR products demonstrated that Anaplasma bovis, Anaplasma capra, and an Ehrlichia species were detected in the H. longicornis with the minimum infection rates (MIR) of 1.11%, 1.32%, and 0.05%, respectively; A. bovis, A. capra, and unnamed Anaplasma sp. were detected in goats with an infection rate of 26.31%, 1.31% and 1.97%, respectively. Anaplasma and Ehrlichia species were not detected from cattle, dogs and R. microplus ticks. The genetic differences in the groEL gene sequences of the Anaplasma in the current study were large, whereas the 16S rRNA and gltA gene sequences were less disparate. This study shows that ticks and goats in Suizhou County, Hubei Province carry multiple Anaplasma species and an Ehrlichia species, with relatively higher infection rate of A. bovis in goats. Our study indicates that multiple Anaplasma and Ehrlichia species exist in ticks and goats in the central China with potential to cause human infection.

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.

Novel betaherpesviruses and gammaherpesviruses in bats from central China.

Herpesviruses are large double-stranded DNA viruses that cause infections in animals and humans with a characteristic of latent infectious within specific tissues. Bats are natural hosts of variety human-infecting viruses and recently have been described as hosts for herpesviruses in several countries around the world. In this study we collected 140 insectivorous bats in the neighboring urban areas of Wuhan City, Hubei Province in the central China between 2020 and 2021. Nested PCR targeting the dpol gene sequence indicated that a total of 22 individuals (15.7% of the sample) tested positive for herpesvirus with 4 strains belonging to the genus Betaherpesvirus and the remaining 18 strains classified as Gammahersvirus. Furthermore, the herpesvirus prevalence in Rhinolophus pusillus was higher at 26.3%, compared to 8.4% in Myotis davidii. The RP701 strain from R. pusillus was the predominant gammaherpesvirus strain detected in bats, accounting for 94.4% (17/18) of all strains. The variations in γ-herpesviruses genomic sequences was evident in phylogenetic tree, where RP701 strain was clustered together with ruminant γ-herpesviruses, while MD704 strain formed a distinct clade with a hedgehog γ-herpesvirus. Four betaherpesviruses exclusively identified from M. davidii, with nucleotide identities ranging from 79.7 to 82.6% compared to known betaherpesviruses. Our study provided evidence that M. davidii can sever as natural host for ß-herpesviruses, which extended the host species range. In conclusion, we found that bats from central China harbored novel ß-herpesviruses and γ-herpesviruses which were phylogenetically related to ruminant γ-herpesvirus and hedgehog γ-herpesvirus. Our study indicates that bats are natural hosts of ß- and γ-herpesviruses and further studies are needed to determine whether there is cross-species transmission of herpesviruses between bats and other animals, or humans.

SFTSV nucleoprotein mediates DNA sensor cGAS degradation to suppress cGAS-dependent antiviral responses.

Cyclic GMP-AMP synthase (cGAS) is an important DNA pattern recognition receptor that senses double-stranded DNA derived from invading pathogens or self DNA in cytoplasm, leading to an antiviral interferon response. A tick-borne Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), is an RNA virus that causes a severe emerging viral hemorrhagic fever in Asia with a high case fatality rate of up to 30%. However, it is unclear whether cGAS interacts with SFTSV infection. In this study, we found that SFTSV infection upregulated cGAS RNA transcription and protein expression, indicating that cGAS is an important innate immune response against SFTSV infection. The mechanism of cGAS recognizing SFTSV is by cGAS interacting with misplaced mitochondrial DNA in the cytoplasm. Depletion of mitochondrial DNA significantly inhibited cGAS activation under SFTSV infection. Strikingly, we found that SFTSV nucleoprotein (N) induced cGAS degradation in a dose-dependent manner. Mechanically, N interacted with the 161-382 domain of cGAS and linked the cGAS to LC3. The cGAS-N-LC3 trimer was targeted to N-induced autophagy, and the cGAS was degraded in autolysosome. Taken together, our study discovered a novel antagonistic mechanism of RNA viruses, SFTSV is able to suppress the cGAS-dependent antiviral innate immune responses through N-hijacking cGAS into N-induced autophagy. Our results indicated that SFTSV N is an important virulence factor of SFTSV in mediating host antiviral immune responses. IMPORTANCE: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne RNA virus that is widespread in East and Southeast Asian countries with a high fatality rate of up to 30%. Up to now, many cytoplasmic pattern recognition receptors, such as RIG-I, MDA5, and SAFA, have been reported to recognize SFTSV genomic RNA and trigger interferon-dependent antiviral responses. However, current knowledge is not clear whether SFTSV can be recognized by DNA sensor cyclic GMP-AMP synthase (cGAS). Our study demonstrated that cGAS could recognize SFTSV infection via ectopic mitochondrial DNA, and the activated cGAS-stimulator of interferon genes signaling pathway could significantly inhibit SFTSV replication. Importantly, we further uncovered a novel mechanism of SFTSV to inhibit innate immune responses by the degradation of cGAS. cGAS was degraded in N-induced autophagy. Collectively, this study illustrated a novel virulence factor of SFTSV to suppress innate immune responses through autophagy-dependent cGAS degradation.