Article
Virology
Xiaorong Meng, Michael Veit
Summary: This study found that the palmitoylation of HA of influenza B virus occurs in the ER, whereas acylation of HA of influenza A virus occurs in the Golgi. The ER-localized DHHCs 1, 2, 4, and 6 are responsible for acylation of HA of influenza B virus, which is different from the enzymes identified for acylation of HA of influenza A virus. The transmembrane region may be critical for the acylation of HA of influenza A and B viruses by different DHHCs.
JOURNAL OF VIROLOGY
(2023)
Article
Multidisciplinary Sciences
Mallory L. Myers, John R. Gallagher, Alexander J. Kim, Walker H. Payne, Samantha Maldonado-Puga, Haralabos Assimakopoulos, Kevin W. Bock, Udana Torian, Ian N. Moore, Audray K. Harris
Summary: Influenza viruses cause worldwide epidemics and yearly reformulation of commercial influenza vaccines (CIV) due to the antigenic variation of Hemagglutinin (HA). This study investigates the structural organization of HA in four current CIVs using electron microscopy, revealing different arrangements including individual HAs, starfish structures, and spiked-nanodisc structures. CIVs with spiked nanodiscs induce the highest levels of cross-reactive antibodies. Therefore, HA structural organization can be an important parameter for CIVs and their efficacy.
NATURE COMMUNICATIONS
(2023)
Review
Cell Biology
Jiayu Jin, Xiuling Zhi, Xinhong Wang, Dan Meng
Summary: Protein palmitoylation, a common lipid modification, plays important roles in regulating protein stability and cellular processes by attaching fatty acid chains to cysteine residues. The reversibility of palmitoylation allows proteins to shuttle rapidly between membranes and the cytoplasm, with mutations in PATs being closely linked to various human diseases.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Microbiology
Dina A. Abdulrahman, Xiaorong Meng, Michael Veit
Summary: Recent pandemics caused by zoonotic coronaviruses and influenza A viruses have shown that viral glycoproteins and ion channels are S-acylated. DHHC family members play a crucial role in palmitoylation, with a common set of DHHCs acylating SARS-CoV-2 and Flu A proteins in human cells. This highlights the potential of DHHCs as targets for broad-spectrum antiviral drugs.
Article
Virology
Danielle Thompson, Christiana Victoria Cismaru, Jean-Sebastien Rougier, Martin Schwemmle, Gert Zimmer
Summary: The proton channel activity of bat influenza A virus (IAV) M2 proteins was found to be low, indicating that they are unable to fully protect acid-sensitive HA protein from conformational changes. The primary sequences of bat IAV M2 proteins also differ significantly from conventional IAV M2 proteins, suggesting possible differences in their biological function. This study reveals the importance of the proton channel activity of bat IAV M2 proteins in virus replication.
JOURNAL OF VIROLOGY
(2023)
Article
Microbiology
Haiying Mao, Lei Cao, Ting Xu, Xiaohan Xia, Peilei Ren, Pengfei Han, Chengfei Li, Xianfeng Hui, Xian Lin, Kun Huang, Meilin Jin
Summary: This study identified a novel host factor, YWHAG, that interacts with the IAV matrix protein M2 and regulates viral budding. Knockout of YWHAG increased viral production, while overexpression reduced the titer of virus progeny.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yingmin Sun, Keyong Du
Summary: The association of AMP-activated protein kinase (AMPK) with membranes is crucial for its activation and function. Protein lipid modification, such as palmitoylation, myristoylation, and farnesylation, plays an important role in regulating protein-membrane interactions. This study focuses on the palmitoylation of AMPK alpha, which is essential for its activation and subcellular compartmentalization. The researchers identified DHHC17 as a candidate palmitoyltransferase for AMPK alpha and found that DHHC17 modulates AMPK membrane association and activation. Knocking out DHHC17 in the liver impaired AMPK activation and hepatic autophagy, leading to a diabetes-like syndrome. These findings highlight the critical role of AMPK alpha palmitoylation in its activation and DHHC17 as a novel regulator of hepatic metabolism.
MOLECULAR AND CELLULAR BIOLOGY
(2022)
Article
Virology
Xiaorong Zhang, Zongyi Bo, Chenchen Meng, Yin Chen, Chengcheng Zhang, Yongzhong Cao, Yantao Wu
Summary: This study developed recombinant NDVs expressing HA using a thermostable NDV vector, which maintained their thermostable and lentogenic nature. Immunization data showed that rAHR09-HA and rAHR09-HAF induced a higher HI antibody titer against H9N2 AIV and NDV, and reduced virus shedding after challenge. These results suggest that rAHR09-HA and rAHR09-HAF may be vaccine candidates against H9N2 AIV.
Article
Agriculture, Dairy & Animal Science
Guanming Shao, Zi Xie, Ming Liang, Yaxin Liu, Chaoyi Song, Keyu Feng, Xinheng Zhang, Wencheng Lin, Jun Fu, Qingmei Xie
Summary: In this study, a recombinant NDV expressing H9N2 AIV HA protein was developed using Red/ET homologous recombination technology. The recombinant virus showed similar replication kinetics with the parent strain and induced high HI antibody titer against H9N2 AIV. In the challenge experiment, the recombinant virus significantly reduced virus shedding and protected the intestinal mucosal epithelial cells.
Article
Medicine, Research & Experimental
Iuliia M. Gilchuk, Sandhya Bangaru, Nurgun Kose, Robin G. Bombardi, Andrew Trivette, Sheng Li, Hannah L. Turner, Robert H. Carnahan, Andrew B. Ward, James E. Crowe Jr
Summary: This study examined the B cell response to H7 HA in individuals who had recovered from natural H7N9 virus infection. Circulating H7-reactive B cells were found to recognize a diverse antigenic landscape on the HA molecule and exhibit broad recognition of unrelated H7 strains. Functional testing of the antibodies revealed diverse patterns of inhibition, including neutralizing and HA trimer-disrupting activities.
Article
Virology
Meng Hu, Jeremy C. Jones, Balaji Banoth, Chet Raj Ojha, Jeri Carol Crumpton, Lisa Kercher, Robert G. Webster, Richard J. Webby, Charles J. Russell
Summary: This study investigated the replication and transmission of swine H1N1 isolates in ferrets, finding that a stabilized HA played a more prominent role than polymerase enhancement in the replication and transmission of the viruses. The results suggest that pandemic risk-assessment studies may benefit from deep sequencing to identify minor variants with human-adapted traits.
JOURNAL OF VIROLOGY
(2022)
Article
Cell Biology
Ujjwal Kumar, Priya Goyal, Zaid K. Madni, Kajal Kamble, Vineet Gaur, Maitreyi S. Rajala, Dinakar M. Salunke
Summary: This study obtained four unique single-chain antibodies against M2e through screening human antibody libraries, which can bind to the conserved site of M2e and the full-length M2 protein expressed on HEK293T cells. The structural and biochemical study showed the binding of these antibodies with M2e peptide dimer, providing insights into their function of recognizing and restricting the release of new viral particles from an infected host cell.
JOURNAL OF BIOMEDICAL SCIENCE
(2023)
Article
Biophysics
Themis Lazaridis
Summary: The M2 proton channel in influenza A virus allows acidification of the virion when external pH is lowered, but does not conduct protons outward when internal pH is lowered. Trp41 and Asp44 residues play a role in preventing pH-driven outward conductance, but the mechanism is unclear. Molecular dynamics simulations reveal that inward proton movement is easier than outward movement when key His37 residues are neutral, and this preference for inward movement increases with increasing charge on His37. Several factors contribute to this asymmetry, including electrostatic interactions, orientation of hydronium ions, and trapping of ions at specific sites in the channel.
BIOPHYSICAL JOURNAL
(2023)
Article
Nanoscience & Nanotechnology
Chunhong Dong, Ye Wang, Wandi Zhu, Yao Ma, Joo Kim, Lai Wei, Gilbert X. Gonzalez, Bao-Zhong Wang
Summary: In this study, PEI-HA/CpG nanoparticles were developed as a potential cross-protective influenza vaccine. The nanoparticles significantly enhanced HA immunogenicity, inducing robust and balanced antibody responses and cellular immune responses. These immune responses remained strong even after six months of observation post-immunization.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Chemistry, Multidisciplinary
Laura C. Watkins, William F. DeGrado, Gregory A. Voth
Summary: The D44N mutation in the influenza A M2 channel opens the channel gate and increases proton conduction, leading to a loss of asymmetric conduction. This mutation lowers the energy barrier for His37 deprotonation in the activated state and facilitates proton flux through the Va127 tetrad. Increased hydration around the His37 tetrad enhances proton transport efficiency.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Cell Biology
Mohamed Rasheed Gadalla, Eliot Morrison, Marina Serebryakova, Xueijiao Han, Thorsten Wolff, Christian Freund, Larisa Kordyukova, Michael Veit
Summary: The study revealed that ZDHHC22 is upregulated in virus-infected cells, particularly with avian influenza virus strains. Knocking out ZDHHC22 gene did not reduce acylation of M2 and HA, indicating its potential involvement in virus replication.
CELLULAR MICROBIOLOGY
(2021)
Article
Microbiology
Minze Zhang, Xiaoliang Han, Klaus Osterrieder, Michael Veit
Summary: The major membrane proteins GP5 and M of porcine reproductive and respiratory syndrome virus are palmitoylated at cysteines, which is essential for virus growth. Acylation is required for the formation of infectious particles and viruses lacking acylation sites show reduced growth in cell culture. Multiple fatty acids attached to GP5 and M are necessary for clustering of dimerized proteins at Golgi membranes and virus assembly.
Article
Immunology
Wan-Ting He, Meng Lu, Gang Xing, Yuekun Shao, Meng Zhang, Yichen Yang, Xinxin Li, Letian Zhang, Gairu Li, Zongxi Cao, Shuo Su, Michael Veit, Haijian He
Summary: Influenza D virus, a novel member of the Orthomyxoviridae, was first isolated from swine but cattle are its primary reservoir. A study on the emergence of IDV in China highlights the potential threat it poses to livestock and farming in the country. Additionally, the diversity and evolutionary dynamics of IDVs in China were analyzed, revealing patterns of local transmission and the presence of distinct sub-lineages.
MICROBIAL PATHOGENESIS
(2021)
Article
Microbiology
Dina A. Abdulrahman, Xiaorong Meng, Michael Veit
Summary: Recent pandemics caused by zoonotic coronaviruses and influenza A viruses have shown that viral glycoproteins and ion channels are S-acylated. DHHC family members play a crucial role in palmitoylation, with a common set of DHHCs acylating SARS-CoV-2 and Flu A proteins in human cells. This highlights the potential of DHHCs as targets for broad-spectrum antiviral drugs.
Article
Biochemistry & Molecular Biology
Xu Zhang, Tim Abel, Shuo Su, Andreas Herrmann, Kai Ludwig, Michael Veit
Summary: The assembly and budding of influenza C virus is mediated by three membrane proteins. The hexagonal arrangement of the HEF protein is crucial for virus budding, and its interaction with CM1 stabilizes the clusters. CM2 and CM1 also play important roles in this process.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Virology
Ningning Wang, Xiaofeng Zhai, Xiaoling Li, Yu Wang, Wan-Ting He, Zhiwen Jiang, Michael Veit, Shuo Su
Summary: The lack of monitoring and vaccines has led to widespread infections of alphaviruses. Getah virus (GETV), a mosquito-borne alphavirus, poses a risk to animals and potentially humans. The identification of residue 253 in the E2 glycoprotein as crucial for viral infection and pathogenesis highlights the importance of understanding the genetic determinants of GETV virulence. The discovery of heparan sulfate (HS) as an attachment factor for GETV, along with the potential for targeted therapies based on residue 253, reveals new insights into the pathogenic mechanisms and treatment options for GETV.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Irina Panina, Nikolay Krylov, Mohamed Rasheed Gadalla, Elena Aliper, Larisa Kordyukova, Michael Veit, Anton Chugunov, Roman Efremov
Summary: Lipid modification of viral proteins plays a crucial role in virus pathogenesis. The study focuses on human DHHC20 enzyme involved in S-protein acylation of SARS-CoV-2. Molecular dynamics simulations reveal that C16 is the preferred acyl chain length for autoacylation by hDHHC20, although the V185G mutant shows preference for C18. Unusual hydrophilic ridge and responsive hydrophilic patch in hDHHC20 and S-protein TM-domain trimer respectively are also found. Mutations in critical residues of the spike protein result in decreased S-acylation. The findings may contribute to the development of inhibitors targeting hDHHC20 for interfering with replication of coronaviruses and other enveloped viruses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Anna Karolina Matczuk, Minze Zhang, Michael Veit, Maciej Ugorski
Summary: Equine arteritis virus (EAV) is a significant pathogen of horses, with its glycoproteins GP2, GP3, and GP4 forming a heterotrimer complex responsible for cellular tropism, making it a potential subunit vaccine candidate for horses.
Review
Cell Biology
Jin Tian, Jiumeng Sun, Dongyan Li, Ningning Wang, Lifang Wang, Chang Zhang, Xiaorong Meng, Xiang Ji, Marc A. Suchard, Xu Zhang, Alexander Lai, Shuo Su, Michael Veit
Summary: This article mainly introduces the taxonomy, geographic distribution, and unique traits of bats as virus reservoirs, as well as the origin, intermediate hosts, and interspecies transmission mechanisms of Middle East respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus, SARS-CoV-2, and other viruses associated with bats. The molecular interactions between viral surface proteins and host cell receptors are also studied, comparing these interactions in humans, intermediate hosts, and bats.
Article
Biochemistry & Molecular Biology
Michael Veit, Mohamed Rasheed Gadalla, Minze Zhang
Summary: This study used the artificial intelligence-based system alphafold2 to predict the structure of Gp5/M in porcine reproductive and respiratory syndrome virus. The predicted structure revealed a dimeric core and an open cavity beneath the membrane, and showed similarities to the M and Orf3a proteins of coronaviruses. The study also discussed the role of Gp5/M in virus replication and the mechanisms of antibody-dependent virus neutralization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Letter
Infectious Diseases
Jiumeng Sun, Ningning Wang, Zhiwen Jiang, Dongyan Li, Jin Zhao, Xinxin Li, Lang Gong, Chang Zhang, Haijian He, Shuo Su, Guihong Zhang, Michael Veit
JOURNAL OF INFECTION
(2023)
Article
Virology
Jin Zhao, Simon Dellicour, Ziqing Yan, Michael Veit, Mandev S. Gill, Wan-Ting He, Xiaofeng Zhai, Xiang Ji, Marc A. Suchard, Philippe Lemey, Shuo Su
Summary: By conducting metagenomic next-generation sequencing, we identified Getah virus as the pathogen responsible for a reemerging swine disease in China. This virus is capable of replicating in various cell lines, including human cells, and demonstrates high pathogenicity in a mouse model. Our study also revealed the impact of environmental factors on the genetic diversity and dispersal of the virus.
JOURNAL OF VIROLOGY
(2023)
Article
Virology
Xiaorong Meng, Michael Veit
Summary: This study found that the palmitoylation of HA of influenza B virus occurs in the ER, whereas acylation of HA of influenza A virus occurs in the Golgi. The ER-localized DHHCs 1, 2, 4, and 6 are responsible for acylation of HA of influenza B virus, which is different from the enzymes identified for acylation of HA of influenza A virus. The transmembrane region may be critical for the acylation of HA of influenza A and B viruses by different DHHCs.
JOURNAL OF VIROLOGY
(2023)
Article
Virology
Wan-Ting He, Dongyan Li, Guy Baele, Jin Zhao, Zhiwen Jiang, Xiang Ji, Michael Veit, Marc A. Suchard, Edward C. Holmes, Philippe Lemey, Maciej F. Boni, Shuo Su
Summary: Through retrospective epidemiological study, new lineages of porcine hemagglutinating encephalomyelitis virus (PHEV) complex coronaviruses (CoVs) were discovered in swine populations in China. These novel lineages cause respiratory symptoms without neurological symptoms typically associated with classical PHEV infection. The novel lineages have been circulating in at least eight provinces in southeastern China.
Meeting Abstract
Biochemistry & Molecular Biology
Larisa V. Kordyukova, Bodan Hu, Marina V. Serebryakova, Michael Veit
