Biology subjects

Wang, Z.-D.

Publications and source records attributed to Wang, Z.-D..

3 recordsLinked to original sources

bioRxiv2024

The segmented flavivirus Alongshan virus reduces mitochondrial mass via degrading STAT2 to suppress innate immune response

Alongshan virus (ALSV) is a newly discovered pathogen of the Flaviviridae family, characterized by a multi-segmented genome distantly related to the canonical flaviviruses. Understanding the pathogenic mechanism of the emerging segmented flavivirus is crucial for the development of intervention strategies. Here we show that ALSV can infect multiple mammalian cells and induces the expression of antiviral genes. Moreover, ALSV is sensitive to IFN-{beta} and possesses the ability to counteract type I IFN response. Mechanistically, ALSVs nonstructural protein NSP1 binds to and degrades human STAT2 through an autophagy pathway in a species-dependent manner, resulting in direct inhibition of the expression of interferon-stimulated genes (ISGs). Specifically, NSP1 methyltransferase domain binds to the key sites of F175/R176 located in coiled-coil domain of STAT2. Moreover, NSP1-mediated degradation of STAT2 results in a reduction in mitochondrial mass by disrupting mitochondrial dynamics to induce mitophagy and inhibiting mitochondrial biogenesis, thereby suppressing the innate immune response. Interestingly, inhibiting mitophagy using 3-Methyladenine and enhancing mitochondrial biogenesis using the PPAR{gamma} agonist pioglitazone can reverse NSP1-mediated inhibition of ISGs, suggesting that promoting mitochondrial mass presents an effective antiviral strategy. Our findings elucidate the intricate regulatory crosstalk between ALSV and the hosts innate immune response, providing valuable insights into the pathogenesis and intervention strategy of emerging segmented flavivirus.

microbiology↗

bioRxiv2023

Pan-sphingolipid profiling reveals differential functions of sphingolipid biosynthesis isozymes of C. elegans

Multiple isozymes are encoded in the C. elegans genome for the various sphingolipid biosynthesis reactions, but the contributions of individual isozymes are characterized only in part. We developed a simple but effective reversed-phase liquid chromatography-tandem mass spectrometry (RPLC-MS/MS) method that enables simultaneous identification and quantification of ceramides (Cer), glucosylceramides (GlcCer), and sphingomyelins (SM), three important classes of sphingolipids from the same MS run. Validating this pan-sphingolipid profiling method, we show that nearly all 47 quantifiable sphingolipid species found in young adult worms were reduced upon RNA interference (RNAi) of sptl-1 or elo-5, which are required for synthesis of the id17:1 sphingoid base. We also confirm that HYL-1 and HYL-2, but not LAGR-1, constitute the major ceramide synthase activity with different preference for fatty acid substrates, and that CGT-3 plays a greater role than CGT-1 does in producing glucosylceramides. Intriguingly, lagr-1 RNAi lowers the abundance of all sphingomyelin species and that of several glucosylceramide species, which suggests that LAGR-1 may have functions beyond what is predicted. Additionally, RNAi of sms-1, -2, and -3 all lower the abundance of sphingomyelins with an odd number of carbon atoms (mostly C21 and C23, with or without hydroxylation) in the N-acyl chain, and only sms-1 RNAi does not elevate sphingomyelins containing even-numbered N-acyl chains. This suggests that sphingolipids containing even-numbered N-acyl chains could be regulated separately, sometimes in opposite directions, with those containing odd-numbered N-acyls, presumably monomethyl branched chain fatty acyls. We also find that ceramide levels are kept in balance with those of glucosylceramides and sphingomyelins.

genetics↗

bioRxiv2020

Identification of a new orthonairovirus associated with human febrile illness in China

The genus Orthonairovirus of the family Nairoviridae includes the important tick-transmitted pathogens, Crimean-Congo hemorrhagic fever virus (CCHFV) and Nairobi sheep disease virus (NSDV), as well as many other poorly characterized viruses isolated from ticks, birds, and mammals1,2. Here we identified a novel orthonairovirus, designated S[o]ngl[i]ng virus (SGLV), from patients who reported being bitten by a tick in China. The genome of SGLV shared similar structural features with orthonairoviruses, with 46.5-65.7% sequence identify. Phylogenetic analysis showed that SGLV belonged to the Tamdy orthonairovirus and formed a unique clade in the Nairoviridae family. Electron microscopy revealed typical morphological characteristics of orthonairoviruses. The isolated SGLVs from the blood samples of patients could induce cytopathic effects in human hepatoma cells. SGLV infection was confirmed in 42 patients in 2017-2018, with the main clinical manifestations of headache, fever, depression, fatigue and dizziness. Serological assays showed that 69% patients generated virus-specific antibody responses in the acute phase. In contrast, neither SGLV viral RNA nor specific antibodies against SGLV were detected in healthy individuals. SGLV was also detected in Ixodes crenulatus, Haemaphysalis longicornis, Haemaphysalis concinna, and Ixodes persulcatus in northeastern China. Collectively, a newly discovered orthonairovirus was shown to be associated with human febrile illness in northeastern China.

microbiology↗