Biology subjects

Weigang, S.

Publications and source records attributed to Weigang, S..

4 recordsLinked to original sources

bioRxiv2025

The antiviral GTPase MxB is packaged into virions and binds via its N-terminal domain to alphaherpesvirus capsids

The interferon-inducible myxovirus resistance proteins belong to the dynamin-like GTPases, with MxA being a restriction factor against several RNA viruses, while MxB restricts infections of lentiviruses and herpesviruses. Humans express MxA(1-662) with an N-terminal domain (NTD) of 43 residues, MxB(1-715) with an NTD of 91 residues, and a truncated MxB(26-715) with an NTD of 66 residues. Although the roles of the GTPase and stalk domains during infection are increasingly elucidated, the function of the different NTDs is not fully understood. Using cell lines stably expressing Mx proteins, we show that MxB(1-715) but not MxA inhibited infection with herpes simplex virus (HSV-1) and pseudorabies virus (PrV). Quantitative mass spectrometry and subviral fractionation experiments indicate that MxB(1- 715) was packaged into the tegument of HSV-1 and PrV virions, but not MxB(26-715) or MxA(1-662). Moreover, we generated recombinant proteins N-terminally fused to different NTD peptides and showed that MxB(1-91), MxB(1-35), and to a lesser extent MxB(26-91) bound to isolated HSV-1 capsids, while MxA(1-43) did not. Our findings indicate that the NTD of MxB is crucial to restrict HSV-1 and PrV infections, that newly assembled virions package MxB into the tegument around the capsid, and that the N-terminal and the C-terminal part of the MxB-NTD contribute to its binding to herpesviral capsids.

molecular biology↗

bioRxiv2022

Optimized intramuscular immunization with VSV-vectored spike protein triggers a superior protective humoral immune response to SARS-CoV-2

Immunization with vesicular stomatitis virus (VSV)-vectored COVID-19 vaccine candidates expressing the SARS-CoV-2 spike protein in place of the VSV glycoprotein relies implicitly on expression of the ACE2 receptor at the muscular injection site. Here, we report that such a viral vector vaccine did not induce protective immunity following intramuscular immunization of K18-hACE2 transgenic mice. However, when the viral vector was trans-complemented with the VSV glycoprotein, intramuscular immunization resulted in high titers of spike-specific neutralizing antibodies. The vaccinated animals were fully protected following infection with a lethal dose of SARS-CoV-2-SD614G via the nasal route, and partially protected if challenged with the SARS-CoV-2Delta variant. While dissemination of the challenge virus to the brain was completely inhibited, replication in the lung with consequent lung pathology was not entirely controlled. Thus, intramuscular immunization was clearly enhanced by trans-complementation of the VSV-vectored vaccines by the VSV glycoprotein and led to protection from COVID-19, although not achieving sterilizing immunity.

immunology↗

bioRxiv2022

The interferon-inducible GTPase MxB promotes capsid disassembly and genome release of herpesviruses

Host proteins sense viral products and induce defence mechanisms, particularly in immune cells. Using cell-free assays and quantitative mass spectrometry, we determined the interactome of capsid- host protein complexes of herpes simplex virus and identified the large dynamin-like GTPase myxovirus resistance protein B (MxB) as an interferon-inducible protein interacting with capsids. Electron microscopy analyses showed that cytosols containing MxB had the remarkable capability to disassemble the icosahedral capsids of herpes simplex viruses and varicella zoster virus into flat sheets of connected triangular faces. In contrast, capsids remained intact in cytosols with MxB mutants unable to hydrolyse GTP or to dimerize. Our data suggest that MxB senses herpesviral capsids, mediates their disassembly, and thereby restricts the efficiency of nuclear targeting of incoming capsids and/or the assembly of progeny capsids. The resulting premature release of viral genomes from capsids may enhance the activation of DNA sensors, and thereby amplify the innate immune responses.

microbiology↗

bioRxiv2020

The landscape of SARS-CoV-2 RNA modifications

In 2019 the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the first documented cases of severe lung disease COVID-19. Since then, SARS-CoV-2 has been spreading around the globe resulting in a severe pandemic with over 500.000 fatalities and large economical and social disruptions in human societies. Gaining knowledge on how SARS-Cov-2 interacts with its host cells and causes COVID-19 is crucial for the intervention of novel therapeutic strategies. SARS-CoV-2, like other coronaviruses, is a positive-strand RNA virus. The viral RNA is modified by RNA-modifying enzymes provided by the host cell. Direct RNA sequencing (DRS) using nanopores enables unbiased sensing of canonical and modified RNA bases of the viral transcripts. In this work, we used DRS to precisely annotate the open reading frames and the landscape of SARS-CoV-2 RNA modifications. We provide the first DRS data of SARS-CoV-2 in infected human lung epithelial cells. From sequencing three isolates, we derive a robust identification of SARS-CoV-2 modification sites within a physiologically relevant host cell type. A comparison of our data with the DRS data from a previous SARS-CoV-2 isolate, both raised in monkey renal cells, reveals consistent RNA modifications across the viral genome. Conservation of the RNA modification pattern during progression of the current pandemic suggests that this pattern is likely essential for the life cycle of SARS-CoV-2 and represents a possible target for drug interventions.

genetics↗