Idrissa Dieng, S. Sagne, Mignane Ndiaye, M. A. Barry, C. Talla, Moufid Mhamadi, Diamilatou Balde, Cheikh Talibouya Touré, B. Diop, A. Sall, G. Fall, C. Loucoubar, O. Faye, O. Faye
{"title":"Detection of human case of dengue virus 2 belonging to sylvatic genotype during routine surveillance of fever in Senegal, Kolda 2021","authors":"Idrissa Dieng, S. Sagne, Mignane Ndiaye, M. A. Barry, C. Talla, Moufid Mhamadi, Diamilatou Balde, Cheikh Talibouya Touré, B. Diop, A. Sall, G. Fall, C. Loucoubar, O. Faye, O. Faye","doi":"10.3389/fviro.2022.1050880","DOIUrl":"https://doi.org/10.3389/fviro.2022.1050880","url":null,"abstract":"Dengue virus 2 (DENV-2) was detected in a febrile patient living in Saré Yoba in the Kolda region of southern Senegal. Phylogenetic analysis based on the full coding region revealed that the virus belongs to the DENV-2 sylvatic genotype and is closely related to a strain (JF260983/99.66% identity) detected in Spain in a tourist who traveled to Guinea-Bissau (which borders the Kolda region) in 2009. This highlights a potential recent under-reported circulation of sylvatic dengue in the southern part of Senegal and calls for reinforced integrated surveillance among humans, non-human primates, and arboreal mosquitoes through a one-health approach.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45224418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyeree Choi, S. Kudchodkar, Ziyang Xu, Michelle Ho, Peng Xiao, S. Ramos, Laurent Humeau, D. Weiner, K. Muthumani
{"title":"Elicitation of immune responses against Nipah virus by an engineered synthetic DNA vaccine","authors":"Hyeree Choi, S. Kudchodkar, Ziyang Xu, Michelle Ho, Peng Xiao, S. Ramos, Laurent Humeau, D. Weiner, K. Muthumani","doi":"10.3389/fviro.2022.968338","DOIUrl":"https://doi.org/10.3389/fviro.2022.968338","url":null,"abstract":"Nipah virus (NiV) is a re-emerging pathogen that causes severe disease in animals and humans. Current treatment measures for NiV infection are insufficient, and there is no approved vaccine against NiV for either humans or animals. Nipah virus is listed as a high-priority pathogen for vaccine and therapeutic research by the World Health Organization (WHO). In the present study, we employed synthetic enhanced DNA technologies developed to design and produce novel consensus NiV Fusion (NiV-F) and Glycoprotein (NiV-G) antigen sequences for inclusion in synthetic DNA vaccines for NiV. The expression of each vaccine antigen was confirmed in vitro using immune-binding assays. Electroporation-enhanced intramuscular injection of each NiV-F and NiV-G into mice induced potent cellular immune responses to multiple epitopes of NiV-G and NiV-F that included antigen-specific CD8+ T cells. Both vaccines elicited high antibody titers in mice, with a single immunization sufficient to seroconvert 100% of immunized animals. Additionally, the NiV-F vaccine also induced antibodies to neutralize NiV-F-pseudotyped virus particles. These data support further study of these novel synthetic enhanced NiV nucleic acid-based antigens as potential components of an effective vaccine against the Nipah virus.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48855561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Beukenhorst, J. Frallicciardi, Clarissa M. Koch, Angela M. Phillips, Michael M. Desai, K. Wichapong, G. Nicolaes, W. Koudstaal, G. Alter, J. Goudsmit
{"title":"The influenza hemagglutinin stem antibody CR9114: Evidence for a narrow evolutionary path towards universal protection","authors":"A. Beukenhorst, J. Frallicciardi, Clarissa M. Koch, Angela M. Phillips, Michael M. Desai, K. Wichapong, G. Nicolaes, W. Koudstaal, G. Alter, J. Goudsmit","doi":"10.3389/fviro.2022.1049134","DOIUrl":"https://doi.org/10.3389/fviro.2022.1049134","url":null,"abstract":"Human monoclonal antibodies (hmAbs) that protect against all influenza A and B strains are considered the road to universal influenza vaccines. Based on publicly-available data, we analyze the mechanistic and structural basis of pan-influenza protection by CR9114, a hemagglutinin (HA) stem-reactive antibody that protects against influenza subtypes from groups A1, A2, and B. The mechanistic basis of CR9114’s universal protection is not limited to in vitro neutralization, as CR9114 also protects in vivo from strains that escape its neutralizing activity: some H2 strains and influenza B. Fusion inhibition, viral egress inhibition, and activation of Fc-mediated effector functions are key contributors to CR9114’s universal protection. A comparative analysis of paratopes – between CR9114 (pan-influenza protection) and structurally similar VH1-69 hmAb CR6261 (influenza A1 protection) – pinpoints the structural basis of pan-influenza protection. CR9114’s heterosubtypic binding is conferred by its ability to bind HA with multiple domains: three HCDR loops and FR3. In contrast to other VH1-69 hmAbs, CR9114 uses a long and polar side chain of tyrosine (Y) residues on its HCDR3 for crucial H-bonds with H3, H5, and B HA. The recognition of a highly conserved epitope by CR9114 results in a high genetic barrier for escape by influenza strains. The nested, hierarchical structure of the mutations between the germline ancestor and CR9114 demonstrates that it is the result of a narrow evolutionary pathway within the B cell population. This rare evolutionary pathway indicates an immuno-recessive epitope and limited opportunity for vaccines to induce a polyclonal CR9114-like response.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47635012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. J. McAllister, Satinder Dahiya, R. Berman, Mackenzie E. Collins, M. Nonnemacher, T. Burdo, B. Wigdahl
{"title":"Altered recruitment of Sp isoforms to HIV-1 long terminal repeat between differentiated monoblastic cell lines and primary monocyte-derived macrophages","authors":"J. J. McAllister, Satinder Dahiya, R. Berman, Mackenzie E. Collins, M. Nonnemacher, T. Burdo, B. Wigdahl","doi":"10.3389/fviro.2022.971293","DOIUrl":"https://doi.org/10.3389/fviro.2022.971293","url":null,"abstract":"Human immunodeficiency virus type 1 (HIV-1) transcription in cells of the monocyte-macrophage lineage is regulated by interactions between the HIV-1 long terminal repeat (LTR) and a variety of host cell and viral proteins. Binding of the Sp family of transcription factors (TFs) to the G/C box array of the LTR governs both basal as well as activated LTR-directed transcriptional activity. The effect of monocytic differentiation on Sp factor binding and transactivation was examined with respect to the HIV-1 LTR. The binding of Sp1, full-length Sp3 and truncated Sp3 to a high affinity HIV-1 Sp element was specifically investigated and results showed that Sp1 binding increased relative to the binding of the sum of full-length and truncated Sp3 binding following chemically-induced monocytic differentiation in monoblastic (U-937, THP-1) and myelomonocytic (HL-60) cells. In addition, Sp binding ratios from PMA-induced cell lines were shown to more closely approximate those derived from primary monocyte-derived macrophages (MDMs) than did ratios derived from uninduced cell lines. The altered Sp binding phenotype associated with changes in the transcriptional activation mediated by the HIV-1 G/C box array. Additionally, analysis of post-translational modifications on Sp1 and Sp3 revealed a loss of phosphorylation on serine and threonine residues with chemically-induced differentiation indicating that the activity of Sp factors is additionally regulated at the level of post-translational modifications (PTMs).","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45273382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leila Issmail, C. Möser, Christian Jäger, Basma Altattan, D. Ramsbeck, M. Kleinschmidt, Mirko Buchholz, David Smith, T. Grunwald
{"title":"Prefusion-specific antibody-derived peptides trivalently presented on DNA-nanoscaffolds as an innovative strategy against RSV entry","authors":"Leila Issmail, C. Möser, Christian Jäger, Basma Altattan, D. Ramsbeck, M. Kleinschmidt, Mirko Buchholz, David Smith, T. Grunwald","doi":"10.3389/fviro.2022.994843","DOIUrl":"https://doi.org/10.3389/fviro.2022.994843","url":null,"abstract":"Human respiratory syncytial virus (RSV) is the primary cause of acute lower respiratory tract infections in children and the elderly worldwide, for which neither a vaccine nor an effective therapy is approved. The entry of RSV into the host cell is mediated by stepwise structural changes in the surface RSV fusion (RSV-F) glycoprotein. Recent progress in structural and functional studies of RSV-F glycoprotein revealed conformation-dependent neutralizing epitopes which have become attractive targets for vaccine and therapeutic development. As RSV-F is present on viral surface in a trimeric form, a trivalent binding interaction between a candidate fusion inhibitor and the respective epitopes on each of the three monomers is expected to prevent viral infection at higher potency than a monovalent or bivalent inhibitor. Here we demonstrate a novel RSV entry inhibitory approach by implementing a trimeric DNA nanostructure as a template to display up to three linear peptide moieties that simultaneously target an epitope on the surface of the prefusion RSV-F protein. In order to design synthetic binding peptides that can be coupled to the DNA nanostructure, the prefusion RSV-F-specific monoclonal antibody (D25) was selected. Complementarity-determining region 3 (CDR3) derived peptides underwent truncation and alanine-scanning mutagenesis analysis, followed by systematic sequence modifications using non-canonical amino acids. The most effective peptide candidate was used as a binding moiety to functionalize the DNA nanostructure. The designed DNA-peptide construct was able to block RSV infection on cells more efficiently than the monomeric peptides, however a more moderate reduction of viral load was observed in the lungs of infected mice upon intranasal application, likely due to dissociation or absorption of the underlying DNA structure by cells in the lungs. Taken together, our results point towards the inhibitory potential of a novel trimeric DNA-peptide based approach against RSV and open the possibility to apply this platform to target other viral infections.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91395031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yukina Uemura, Ayaka Ohashi, M. Yoshimori, Miwako Nishio, T. Hirakawa, N. Shimizu, Naomi Wada, K. Imadome, A. Arai
{"title":"Plasma interferon-γ concentration: a potential biomarker of disease activity of systemic chronic active Epstein-Barr virus infection","authors":"Yukina Uemura, Ayaka Ohashi, M. Yoshimori, Miwako Nishio, T. Hirakawa, N. Shimizu, Naomi Wada, K. Imadome, A. Arai","doi":"10.3389/fviro.2022.999929","DOIUrl":"https://doi.org/10.3389/fviro.2022.999929","url":null,"abstract":"Systemic chronic active Epstein-Barr virus infection (sCAEBV) is an intractable disease that present activated EBV-infected T- or NK-cells and their clonal proliferation. When inflammatory symptoms persist and proceed, a lethal complication of hemophagocytic lymphohistiocytosis (HLH) develops, but its biomarker to represent the pathophysiology and an effective agent to cure have not been developed as of today. It is known that interferon-γ (IFN-γ) level in the peripheral blood increases in HLH correlatedly with the disease condition and that antagonistic anti-IFN-γ antibody is effective against HLH. We examined the plasma level of IFN-γ to investigate its role in the disease condition of sCAEBV. sCAEBV was diagnosed based on the criteria conforming to the definition of sCAEBV in the WHO classification issued in 2017. As it was previously reported, disease activity was defined as the condition positive for any one of the followings: fever, liver dysfunction, progressive skin lesions, vasculitis, and uveitis. Eighteen sCAEBV patients were examined. Their plasma IFN-γ levels were significantly higher than those of healthy donors. The levels in sCAEBV patients with disease activity were higher than those without disease activity. The mRNA expression of IFNG was detected in EBV-infected cells of all patients. We also detected a correlation between plasma IFN-γ levels and mRNA levels of EBV-infected cells in peripheral blood mononuclear cells. These results suggest that EBV-infected cells produce IFN-γ in sCAEBV. Although the difference was not significant, the patients whose plasma IFN-γ levels at diagnosis were higher than 40 pg/mL tended to result in poorer survival than those with lower levels. We concluded that plasma IFN-γ is a potential biomarker that indicates disease activity of sCAEBV. Further study shall confirm its significance.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49314960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samuel Narvey, Alex Vandenakker, Megan Rempel, R. Douville
{"title":"Predicted cellular interactors of the endogenous retrovirus-K protease enzyme","authors":"Samuel Narvey, Alex Vandenakker, Megan Rempel, R. Douville","doi":"10.3389/fviro.2022.972156","DOIUrl":"https://doi.org/10.3389/fviro.2022.972156","url":null,"abstract":"Retroviral proteases are essential enzymes for viral replication and drive changes within the cellular proteome. While several studies have demonstrated that protease (PR) enzymes from exogenous retroviruses cleave cellular proteins and modulate cellular signaling, the impact of PRs encoded by endogenous retroviruses within the human genome has been largely overlooked. One human symbiont called Endogenous retrovirus-K (ERVK) is pathologically associated with both neurological disease and cancers. Using a computational biology approach, we sought to characterize the ERVK PR interactome. The ERVK PR protein sequence was analyzed using the Eukaryotic Linear Motif (ELM) database and results compared to ELMs of other betaretroviral PRs and similar endogenated viral PRs. A list of putative ERVK PR cellular protein interactors was curated from the ELM list and submitted for STRING analysis to generate an ERVK PR interactome. Reactome analysis was used to identify key pathways potentially influenced by ERVK PR. Network analysis postulated that ERVK PR interacts at the apex of several ubiquitination pathways, as well as has a role in the DNA damage response, gene regulation, and intracellular trafficking. Among retroviral PRs, a predicted interaction with proliferating cell nuclear antigen (PCNA) was unique to ERVK PR. The most prominent disease-associated pathways identified were viral carcinogenesis and neurodegeneration. This strengthens the role of ERVK PR in these pathologies by putatively driving alterations in cellular signaling cascades via select protein-protein interactions.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41320394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}