scholarly journals Glycosylation of ALV-J envelope protein at sites 17 and 193 is pivotal in the virus replication

2021 ◽  
Author(s):  
Moru Xu ◽  
Kun Qian ◽  
Hongxia Shao ◽  
Yongxiu Yao ◽  
Venugopal Nair ◽  
...  
Keyword(s):  
Virus Replication ◽  
Receptor Binding ◽  
Envelope Protein ◽  
Protein Function ◽  
Protein Processing ◽  
Infection Process ◽  
Systematic Research ◽  
Virion Incorporation ◽  
Env Protein ◽  
Tibetan Chicken

Glycans on envelope glycoprotein (Env) of the subgroup J avian leukosis virus (ALV-J) play an essential role in virion integrity and infection process. In this study, we found that among the 13 predicted N-linked glycosylation sites (NGSs) in gp85 of Tibetan chicken strain TBC-J6, N17 and N193/N191 are pivotal in the virus replication. Further research illustrated that mutation at N193 weakened Env-receptor binding in blocking assay of viral entrance, co-immunoprecipitation and ELISA. Our studies also showed that N17 was involved in Env protein processing and later virion incorporation, based on the detection of p27 and Env protein in the supernatant and gp37 in the cell culture. This report is a systematic research on clarifying the biological function of NGSs on ALV-J gp85 , which would provide valuable insights in the role of gp85 in ALV life cycle as well as anti-ALV-J strategies. Importance ALV-J is a retrovirus that can cause multiple types of tumors in chickens. Among all the viral proteins, the heavily glycosylated envelope protein is especially crucial. Glycosylation plays a major role in Env protein function, including protein processing, receptor attachment and immune evasion. Notably, viruses isolated recently seem to lose the 6 th and 11 st NGSs, which are proved to be important in receptor binding. In our study, the 1 st (N17) and 8 th (N193) NGS of gp85 of strain TBC-J6 can largely influence the titer of this virus. Deglycosylation at N193 weakened Env-receptor binding, while mutation at N17 influenced Env protein processing. This study systemically analyzed the function of NGSs in ALV-J in different aspects, which may help us to understand the lifecycle of ALV-J and provide antiviral targets for the control of ALV-J.

scholarly journals The key amino acids of E protein involved in early flavivirus infection: viral entry

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tao Hu ◽  
Zhen Wu ◽  
Shaoxiong Wu ◽  
Shun Chen ◽  
Anchun Cheng
Keyword(s):  
Amino Acids ◽  
Conformational Changes ◽  
Viral Entry ◽  
Envelope Protein ◽  
Cell Attachment ◽  
Envelope Proteins ◽  
Infection Process ◽  
Early Infection ◽  
Protein Amino Acids ◽  
Α Helix

AbstractFlaviviruses are enveloped viruses that infect multiple hosts. Envelope proteins are the outermost proteins in the structure of flaviviruses and mediate viral infection. Studies indicate that flaviviruses mainly use envelope proteins to bind to cell attachment receptors and endocytic receptors for the entry step. Here, we present current findings regarding key envelope protein amino acids that participate in the flavivirus early infection process. Among these sites, most are located in special positions of the protein structure, such as the α-helix in the stem region and the hinge region between domains I and II, motifs that potentially affect the interaction between different domains. Some of these sites are located in positions involved in conformational changes in envelope proteins. In summary, we summarize and discuss the key envelope protein residues that affect the entry process of flaviviruses, including the process of their discovery and the mechanisms that affect early infection.

scholarly journals In SilicoApproach towards Designing Virtual Oligopeptides for HRSV

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Ruchi Jain ◽  
Shanmughavel Piramanayagam
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Virus Replication ◽  
Lower Respiratory Tract ◽  
Specific Interaction ◽  
Infection Process ◽  
Rational Choices ◽  
Respiratory Tract Illness ◽  
Syncytial Virus ◽  
Infants And Young Children

HRSV (human respiratory syncytial virus) is a serious cause of lower respiratory tract illness in infants and young children. Designing inhibitors from the proteins involved in virus replication and infection process provides target for new therapeutic treatments. In the present study,in silicodocking was performed using motavizumab as a template to design motavizumab derived oligopeptides for developing novel anti-HRSV agents. Additional simulations were conducted to study the conformational propensities of the oligopeptides and confirmed the hypothesis that the designed oligopeptide is highly flexible and capable of assuming stable confirmation. Our study demonstrated the best specific interaction of GEKKLVEAPKS oligopeptide for glycoprotein strain A among various screened oligopeptides. Encouraged by the results, we expect that the proposed scheme will provide rational choices for antibody reengineering which is useful for systematically identifying the possible ways to improve efficacy of existing antibody drugs.

scholarly journals A Single Mutation at Position 156 in the Envelope Protein of Tembusu Virus Is Responsible for Virus Tissue Tropism and Transmissibility in Ducks

2018 ◽  
Vol 92 (17) ◽  
Author(s):  
Dawei Yan ◽  
Ying Shi ◽  
Haiwang Wang ◽  
Guoxin Li ◽  
Xuesong Li ◽  
...  
Keyword(s):  
Amino Acid ◽  
Virus Replication ◽  
Envelope Protein ◽  
Tissue Tropism ◽  
Single Mutation ◽  
Mosquito Vectors ◽  
E Protein ◽  
Virus West Nile ◽  
Tembusu Virus ◽  
Domain I

ABSTRACT Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently. To date, why these flaviviruses can be transmitted without mosquito vectors remains poorly understood. To explore the key molecular basis of flavivirus transmissibility, we compared virus replication and transmissibility of an early and a recent TMUV in ducks. The recent TMUV strain FX2010 replicated systemically and transmitted efficiently in ducks, while the replication of early strain MM1775 was limited and did not transmit among ducks. The TMUV envelope protein and its domain I were responsible for tissue tropism and transmissibility. The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of “150 loop” of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks. These data indicate that the 156S in the envelope protein is critical for TMUV tissue tropism and transmissibility in ducks in the absence of mosquitos. Our findings provide novel insights on understanding TMUV transmission among ducks. IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors. We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks. The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of “150 loop” of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks. Our findings provide new knowledge about TMUV transmission among ducks.

scholarly journals Flavivirus Envelope Protein Glycosylation: Impacts on Viral Infection and Pathogenesis

2020 ◽  
Vol 94 (11) ◽  
Author(s):  
Derek L. Carbaugh ◽  
Helen M. Lazear
Keyword(s):  
Cell Surface ◽  
Viral Infection ◽  
Virus Replication ◽  
Envelope Protein ◽  
Current Knowledge ◽  
Protein Glycosylation ◽  
Surface Attachment ◽  
Virulence Determinant ◽  
Glycosylation Sites ◽  
Virus Interactions

ABSTRACT Flaviviruses encode one, two, or no N-linked glycosylation sites on their envelope proteins. Glycosylation can impact virus interactions with cell surface attachment factors and also may impact virion stability and virus replication. Envelope protein glycosylation has been identified as a virulence determinant for multiple flaviviruses, but the mechanisms by which glycosylation mediates pathogenesis remain unclear. In this Gem, we summarize current knowledge on flavivirus envelope protein glycosylation and its impact on viral infection and pathogenesis.

scholarly journals Retroviral Env Glycoprotein Trafficking and Incorporation into Virions

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Tsutomu Murakami
Keyword(s):  
Infectious Virus ◽  
Structural Data ◽  
Host Factors ◽  
Structural Protein ◽  
Gag Protein ◽  
Virus Particles ◽  
Virion Incorporation ◽  
Actual Mechanism ◽  
Env Protein ◽  
Env Glycoprotein

Together with the Gag protein, the Env glycoprotein is a major retroviral structural protein and is essential for forming infectious virus particles. Env is synthesized, processed, and transported to certain microdomains at the plasma membrane and takes advantage of the same host machinery for its trafficking as that used by cellular glycoproteins. Incorporation of Env into progeny virions is probably mediated by the interaction between Env and Gag, in some cases with the additional involvement of certain host factors. Although several general models have been proposed to explain the incorporation of retroviral Env glycoproteins into virions, the actual mechanism for this process is still unclear, partly because structural data on the Env protein cytoplasmic tail is lacking. This paper presents the current understanding of the synthesis, trafficking, and virion incorporation of retroviral Env proteins.

scholarly journals Role of BC loop residues in structure, function and antigenicity of the West Nile virus envelope protein receptor-binding domain III

Virology ◽  
2010 ◽  
Vol 403 (1) ◽  
pp. 85-91 ◽  
Author(s):  
Shuliu Zhang ◽  
Evgeniy I. Bovshik ◽  
Rodrigo Maillard ◽  
Gregory D. Gromowski ◽  
David E. Volk ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Receptor Binding ◽  
Envelope Protein ◽  
Receptor Binding Domain ◽  
Virus Envelope ◽  
The West ◽  
Protein Receptor ◽  
Virus Envelope Protein ◽  
Domain Iii

scholarly journals HIV-1 Lethality and Loss of Env Protein Expression Induced by Single Synonymous Substitutions in the Virus Genome Intronic-Splicing Silencer

2020 ◽  
Vol 94 (21) ◽  
Author(s):  
Ana Jordan-Paiz ◽  
Maria Nevot ◽  
Kevin Lamkiewicz ◽  
Marie Lataretu ◽  
Sandra Franco ◽  
...  
Keyword(s):  
Protein Expression ◽  
Codon Usage ◽  
Virus Replication ◽  
Synonymous Codon ◽  
Replication Capacity ◽  
Coding Region ◽  
Cpg Dinucleotides ◽  
Splicing Silencer ◽  
Env Protein ◽  
Hiv 1

ABSTRACT Synonymous genome recoding has been widely used to study different aspects of virus biology. Codon usage affects the temporal regulation of viral gene expression. In this study, we performed synonymous codon mutagenesis to investigate whether codon usage affected HIV-1 Env protein expression and virus viability. We replaced the codons AGG, GAG, CCU, ACU, CUC, and GGG of the HIV-1 env gene with the synonymous codons CGU, GAA, CCG, ACG, UUA, and GGA, respectively. We found that recoding the Env protein gp120 coding region (excluding the Rev response element [RRE]) did not significantly affect virus replication capacity, even though we introduced 15 new CpG dinucleotides. In contrast, changing a single codon (AGG to CGU) located in the gp41 coding region (HXB2 env position 2125 to 2127), which was included in the intronic splicing silencer (ISS), completely abolished virus replication and Env expression. Computational analyses of this mutant revealed a severe disruption in the ISS RNA secondary structure. A variant that restored ISS secondary RNA structure also reestablished Env production and virus viability. Interestingly, this codon variant prevented both virus replication and Env translation in a eukaryotic expression system. These findings suggested that disrupting mRNA splicing was not the only means of inhibiting translation. Our findings indicated that synonymous gp120 recoding was not always deleterious to HIV-1 replication. Importantly¸ we found that disrupting an external ISS loop strongly affected HIV-1 replication and Env translation. IMPORTANCE Synonymous substitutions can influence virus phenotype, replication capacity, and virulence. In this study, we explored how synonymous codon mutations impacted HIV-1 Env protein expression and virus replication capacity. We changed a single codon, AGG to CGU, which was located in the gp41 coding region (env nucleotide residues 2125 to 2127) and was included in the HIV-1 intronic splicing silencer. This change completely abolished virus replication and Env expression. We also found that changing codon usage in the gp120 region by including an increased number of CpG dinucleotides did not significantly affect Env expression or virus viability. Our findings showed that synonymous recoding was useful for altering viral phenotype and exploring virus biology.

scholarly journals Immune Escape Adaptive Mutations in the H7N9 Avian Influenza Hemagglutinin Protein Increase Virus Replication Fitness and Decrease Pandemic Potential

2020 ◽  
Vol 94 (19) ◽  
Author(s):  
Pengxiang Chang ◽  
Joshua E. Sealy ◽  
Jean-Remy Sadeyen ◽  
Sushant Bhat ◽  
Deimante Lukosaityte ◽  
...  
Keyword(s):  
Thermal Stability ◽  
Avian Influenza ◽  
Virus Replication ◽  
Receptor Binding ◽  
Immune Escape ◽  
Influenza Viruses ◽  
Escape Mutant ◽  
Hemagglutinin Protein ◽  
Ha Protein ◽  
The Impact

ABSTRACT H7N9 avian influenza viruses (AIVs) continue to evolve and remain a huge threat to human health and the poultry industry. Previously, serially passaging the H7N9 A/Anhui/1/2013 virus in the presence of homologous ferret antiserum resulted in immune escape viruses containing amino acid substitutions alanine to threonine at residues 125 (A125T) and 151 (A151T) and leucine to glutamine at residue 217 (L217Q) in the hemagglutinin (HA) protein. These HA mutations have also been found in field isolates in 2019. To investigate the potential threat of serum escape mutant viruses to humans and poultry, the impact of these HA substitutions, either individually or in combination, on receptor binding, pH of fusion, thermal stability, and virus replication were investigated. Our results showed the serum escape mutant formed large plaques in Madin-Darby canine kidney (MDCK) cells and grew robustly in vitro and in ovo. They had a lower pH of fusion and increased thermal stability. Of note, the serum escape mutant completely lost the ability to bind to human-like receptor analogues. Further analysis revealed that N-linked glycosylation, as a result of A125T or A151T substitutions in HA, resulted in reduced receptor-binding avidity toward both human and avian-like receptor analogues, and the A125T+A151T mutations completely abolished human-like receptor binding. The L217Q mutation enhanced the H7N9 acid and thermal stability while the A151T mutation dramatically decreased H7N9 HA thermal stability. To conclude, H7N9 AIVs that contain A125T+A151T+L217Q mutations in the HA protein may pose a reduced pandemic risk but remain a heightened threat for poultry. IMPORTANCE Avian influenza H7N9 viruses have been causing disease outbreaks in poultry and humans. We previously determined that propagation of H7N9 virus in virus-specific antiserum gives rise to mutant viruses carrying mutations A125T+A151T+L217Q in their hemagglutinin protein, enabling the virus to overcome vaccine-induced immunity. As predicted, these immune escape mutations were also observed in the field viruses that likely emerged in the immunized or naturally exposed birds. This study demonstrates that the immune escape mutants also (i) gained greater replication ability in cultured cells and in chicken embryos as well as (ii) increased acid and thermal stability but (iii) lost preferences for binding to human-type receptor while maintaining binding for the avian-like receptor. Therefore, they potentially pose reduced pandemic risk. However, the emergent virus variants containing the indicated mutations remain a significant risk to poultry due to antigenic drift and improved fitness for poultry.

Sign in / Sign up

Export Citation Format

Share Document