Journal of Virology最新文献

{"title":"Quorum sensing inhibits phage infection by regulating biofilm formation of <i>P. aeruginosa</i> PAO1.","authors":"Lei Cao, Jinhui Mi, Yile He, Guanhua Xuan, Jingxue Wang, Mengzhe Li, Yigang Tong","doi":"10.1128/jvi.01872-24","DOIUrl":"10.1128/jvi.01872-24","url":null,"abstract":"<p><p>Quorum sensing (QS) can regulate diverse critical phenotypic responses in <i>Pseudomonas. aeruginosa</i> (<i>P. aeruginosa</i>), enabling bacterial adaptation to external environmental fluctuations and optimizing population advantages. While there is emerging evidence of QS's involvement in influencing phage infections, our current understanding remains limited, necessitating further investigation. In this study, we isolated and characterized a novel phage designated as BUCT640 that infected <i>P. aeruginosa</i> PAO1. This phage belonged to class <i>Caudoviricetes</i>, genus <i>Bruynoghevirus</i>, with a podovirus morphology, and its adsorption was dependent on Psl polysaccharides, a repeating pentamer used to support biofilm structure. Leveraging phage BUCT640 as a model, we analyzed the role of both <i>rhl</i> QS and <i>las</i> QS in bacteria-phage interactions. Based on its distinctive plaque formation performances on different QS-related mutants, we investigated the variations of phage sensitivity to these strains and ultimately elucidated the mechanism underlying how QS inhibited phage infection to PAO1. Specifically, we unveiled that the <i>las</i> QS could inhibit phage adsorption, which is related to the thickness change caused by biofilm differentiation. Our findings suggest that the inhibition of QS may enhance phage infectivity, potentially facilitating advanced phage therapy combined with QS interference.</p><p><strong>Importance: </strong>Phage therapy is a powerful solution to combat drug-resistant pathogenic bacterial infections and has earned remarkable success in clinical treatment. However, recent insights underscore the potential impact of bacterial QS on phage infection dynamics. Here, we reported a unique phenomenon wherein QS, particularly in the <i>las</i> QS pathway, showed distinctive plaque formation behaviors by enlarging halos around plaques in mutant strains. In addition to this, we first elucidated the correlation between biofilm formation and phage infection. Notably, the <i>las</i> QS could inhibit phage adsorption, an effect closely related to biofilm thickness. Such research could be the evidence to steer bacterial QS toward favorable therapeutical outcomes. Therefore, our work can extend the comprehension of the interactions between bacteria and phages influenced by QS, thereby providing new perspectives on leveraging QS interference to enhance the efficacy of phage therapy for clinical applications.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0187224"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of cytokeratin and cytokine/chemokine expression following influenza virus infection of differentiated human tonsillar epithelial cells.","authors":"S Scott Perry, David C Brice, Ahmed Atef Sakr, Ahmed Kandeil, Jennifer DeBeauchamp, Mohamed Ghonim, Jeremy Jones, Lance Miller, Kasi Vegesana, Jeremy Chase Crawford, Deanna M Langfitt, Lisa Kercher, Hossam A Abdelsamed, Robert G Webster, Paul G Thomas, Richard J Webby, Faten A Okda","doi":"10.1128/jvi.01460-24","DOIUrl":"10.1128/jvi.01460-24","url":null,"abstract":"<p><p>The tonsils have been identified as a site of replication for Epstein-Barr virus, adenovirus, human papillomavirus, and other respiratory viruses. Human tonsil epithelial cells (HTECs) are a heterogeneous group of actively differentiating cells. Here, we investigated the cellular features and susceptibility of differentiated HTECs to specific influenza viruses, including expression of avian-type and mammalian-type sialic acid (SA) receptors, viral replication dynamics, and the associated cytokine secretion profiles. We found that differentiated HTECs possess more abundant α2,3-linked SA (preferentially bound by avian influenza viruses) than α2,6-linked SA (preferentially bound by mammalian strains). This dual receptor expression suggests a role in influenza virus adaptation and tropism within the tonsils by facilitating the binding and entry of multiple influenza virus strains. Our results indicated the susceptibility of differentiated HTECs to a wide range of influenza viruses from human, swine, and avian hosts. Virus production for most strains was detected as early as 1 day post-infection (dpi), and typically peaked by 3 dpi. However, pandemic H1N1 virus showed remarkably delayed replication kinetics that did not peak until at least 7 dpi. Notably, influenza virus infection impacted the expression of cytokeratins in HTEC cultures, which correlated with altered cytokine secretion patterns. These patterns varied within the strains but were most distinct in swine H3N2 infection. In conclusion, differentiated HTECs exhibited a strain-specific pattern of influenza virus replication and innate immune responses that included changes in cytokeratin and cytokine expression. These studies shed light on the complex interplay between influenza viruses and host cells in the tonsils.</p><p><strong>Importance: </strong>To develop effective interventions against influenza, it is important to identify host factors affecting pathogenesis and immune responses. Tonsils are lymphoepithelial organs characterized by infiltration of B and T lymphocytes into the squamous epithelium of tonsillar crypts, beneath which germinal centers play key roles in antigen processing and the immune response. Influenza virus tropism in the human upper respiratory tract is a key determinant of host-range, pathogenesis, and transmission. Accordingly, experimental models using primary cells from the human respiratory tract are relevant for assessing virus tropism and replication competence. Our study addresses the dynamics of influenza virus replication in HTECs, including cellular tropism, infectivity, and cytokeratin and cytokine expression. The results of this study highlight the complex interplay between structural proteins and immune signaling pathways, all of which provide valuable insights into host-virus interactions.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0146024"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostaglandin D2 delays CD8+ T-cell responses and respiratory syncytial virus clearance in geriatric cotton rats.","authors":"Jonathan L Miller, Cameron Leedale, Danyue Kang, Jingtao Lilue, Olivia E Harder, Stefan Niewiesk","doi":"10.1128/jvi.01863-24","DOIUrl":"10.1128/jvi.01863-24","url":null,"abstract":"<p><p>Respiratory syncytial virus (RSV) infection is associated with increased rates of severe disease, hospitalization, and death in elderly individuals. Clearance of RSV is frequently delayed within this demographic, contributing to the more severe disease course. Geriatric cotton rats mimic this prolonged clearance kinetic and serve as a useful animal model for studying age-associated immunological deficits during RSV infection. Treatment with the cyclooxygenase (COX) inhibitor ibuprofen restores RSV clearance, indicating that inflammation contributes to impaired clearance in geriatric cotton rats. Here, we further characterize a compromised immune response in geriatric cotton rats and identify an inflammatory pathway that contributes to this deficiency. Dendritic cell (DC) activation and migration to mediastinal lymph nodes are decreased during early infection in geriatric cotton rats, resulting in delayed generation of cytotoxic T cells and virus clearance. Prostaglandin D₂ (PGD2), which reduces DC migration through the elevation of D-type prostanoid 1 receptor (DP1 receptor), is elevated in the airways of infected geriatric cotton rats. Reducing PGD2 production by inhibiting COX-2 or PGD2 synthase improves RSV clearance kinetics through DC activation and RSV-specific CD8+ T-cell responses in geriatric cotton rats, whereas activation of DP1 receptor through an agonist resulted in delayed viral clearance in adult cotton rats. These results indicate that PGD2 contributes to delayed antigen presentation and CD8+ T-cell responses to RSV in geriatric cotton rats. Inhibiting PGD2 generation or signaling may be a useful mechanism of therapeutic intervention in elderly individuals.IMPORTANCEElderly adults are at increased risk of severe disease resulting from infection with respiratory syncytial virus (RSV), characterized in part by delayed clearance (removal of the virus from airways). Understanding the immunological factors that lead to this delayed clearance may allow for the development of therapies to improve disease outcomes in elderly individuals infected with RSV and other respiratory viruses. Here, we describe an inflammatory pathway in geriatric cotton rats, the preferred small animal laboratory model for RSV, that impairs the generation of an effective immune response. We show that inhibiting this inflammatory pathway in geriatric cotton rats improves immune parameters and speeds clearance of RSV. These results contribute to our understanding of delayed RSV clearance in elderly individuals with possible applications for improving immune responses to RSV in clinical settings.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0186324"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resistance mutations that distinguish HIV-1 envelopes with discordant VRC01 phenotypes from multi-lineage infections in the HVTN703/HPTN081 trial: implications for cross-resistance.","authors":"Paula Cohen, Bronwen E Lambson, Nonhlanhla N Mkhize, Chivonne Moodley, Anna E J Yssel, Thandeka Moyo-Gwete, Talita York, Asanda Gwashu-Nyangiwe, Nonkululeko Ndabambi, Ruwayhida Thebus, Michal Juraska, Allan C deCamp, Brian D Williamson, Craig A Magaret, Peter B Gilbert, Dylan Westfall, Wenjie Deng, James I Mullins, Lynn Morris, Carolyn Williamson, Penny L Moore","doi":"10.1128/jvi.01730-24","DOIUrl":"10.1128/jvi.01730-24","url":null,"abstract":"<p><p>The Antibody Mediated Prevention (AMP) trials showed that passively infused VRC01, a broadly neutralizing antibody (bNAb) targeting the CD4 binding site (CD4bs) on the HIV-1 envelope protein (Env), protected against neutralization-sensitive viruses. We identified six individuals from the VRC01 treatment arm with multi-lineage breakthrough HIV-1 infections from HVTN703, where one variant was sensitive to VRC01 (IC₅₀ < 25 ug/mL) but another was resistant. By comparing Env sequences of resistant and sensitive clones from each participant, we identified sites predicted to affect VRC01 neutralization and assessed the effect of their reversion in the VRC01-resistant clone on neutralization sensitivity. In four pairs, a single mutation restored partial or full sensitivity to VRC01, whereas in the fifth participant, transfer of the entire [Formula: see text]23-V5 loop was required. No VRC01 resistance mutations could be identified in the sixth participant, with the discordant clones differing by >100 amino acids. Mutations responsible for the differential neutralization phenotypes occurred at distinct sites across Env, including residues in loop D, the CD4-binding loop, and between the [Formula: see text]23 and V5 loops. Analysis of deep sequencing <i>env</i> data showed that VRC01 resistance was likely the property of the acquired virus, rather than occurring through post-acquisition evolution. Although VRC01-resistant parental clones generally retained sensitivity to other CD4-binding site bNAbs, they were less potently neutralized than the VRC01-sensitive clones. In conclusion, VRC01 resistance mutations occurred through multiple mutational pathways, but sensitivity to second-generation CD4bs bNAbs was retained even in VRC01-resistant transmitted viruses, confirming the potential of these bNAbs for HIV-1 prevention studies.IMPORTANCEThe Antibody Mediated Prevention (AMP) trials provided proof of principle that VRC01, a CD4-binding site (CD4bs) HIV-1 broadly neutralizing antibody (bNAb), prevented the acquisition of antibody-sensitive viruses. However, understanding common mutations that confer resistance to different bNAbs provides important insights into the genetic barrier to resistance. Here we studied six AMP trial participants with breakthrough infections mediated by multiple viral lineages with discordant VRC01 sensitivity. We identified different mutations across the CD4-binding site that conferred resistance to VRC01 and showed that these mutations were a property of the acquired virus, rather than a result of post-acquisition evolution. We found that although VRC01 resistance was associated with reduced neutralization potency of second-generation CD4-binding site bNAbs, overall neutralization sensitivity was generally retained, which is promising for future use of such bNAbs in clinical trials.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0173024"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaccinia growth factor-dependent modulation of the mTORC1-CAD axis upon nutrient restriction.","authors":"Lara Dsouza, Anil Pant, Blake Pope, Zhilong Yang","doi":"10.1128/jvi.02110-24","DOIUrl":"10.1128/jvi.02110-24","url":null,"abstract":"<p><p>The molecular mechanisms by which vaccinia virus (VACV), the prototypical member of the poxviridae family, reprograms host cell metabolism remain largely unexplored. Additionally, cells sense and respond to fluctuating nutrient availability, thereby modulating metabolic pathways to ensure cellular homeostasis. Understanding how VACV modulates metabolic pathways in response to nutrient signals is crucial for understanding viral replication mechanisms, with the potential for developing antiviral therapies. In this study, we establish the importance of <i>de novo</i> pyrimidine synthesis during VACV infection. We report the significance of vaccinia growth factor (VGF), a viral early protein and a homolog of cellular epidermal growth factor (EGF), in enabling VACV to phosphorylate the key enzyme CAD of the <i>de novo</i> pyrimidine pathway at serine 1859, a site known to positively regulate CAD activity. Although nutrient-poor conditions typically inhibit mTORC1 activation, VACV activates CAD via the mTORC1-S6K1 signaling axis in a VGF-dependent manner, especially upon glutamine and asparagine limitation. However, unlike its cellular homolog EGF, the VGF peptide alone, in the absence of VACV infection, has minimal ability to activate CAD. This suggests the involvement of other viral factors yet to be identified. Our research provides a foundation for understanding the regulation of a significant metabolic pathway, <i>de novo</i> pyrimidine synthesis during VACV infection, shedding new light on viral regulation under distinct nutritional environments. This study not only has the potential to contribute to the advancement of antiviral treatments but also improve the development of VACV as an oncolytic agent and vaccine vector.IMPORTANCEViruses often reprogram host cell metabolism to facilitate replication. How poxviruses, such as the prototype member, vaccinia virus (VACV), modulate host cell metabolism is not well understood. Understanding how VACV affects these metabolic pathways is key to learning about viral replication and developing antiviral treatments. This study highlights the importance of <i>de novo</i> pyrimidine synthesis during VACV infection. We found that the vaccinia growth factor (VGF), a viral protein similar to the cellular epidermal growth factor (EGF), helps VACV activate the enzyme CAD of the <i>de novo</i> pyrimidine pathway. Upon nutrient limitation, VGF is needed for the activation of CAD through mTORC1-S6K signaling. VGF peptide alone is unable to activate this pathway independent of infection, suggesting the involvement of other viral factor(s). Our research not only sheds light on how VACV regulates metabolism but also holds promise for improving VACV as a cancer treatment and vaccine.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0211024"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of N⁶-methyladenosine (m⁶A) mRNA modifications in herpesvirus infections.","authors":"Ruth Verhamme, Herman W Favoreel","doi":"10.1128/jvi.01723-24","DOIUrl":"10.1128/jvi.01723-24","url":null,"abstract":"<p><p>Herpesviruses, a family of large enveloped DNA viruses, establish persistent infections in a wide range of hosts. This characteristic requires an intricate network of interactions with their hosts and host cells. In recent years, the interplay between herpesviruses and the epitranscriptome-chemical modifications in transcripts that may affect mRNA biology and fate-has emerged as a novel aspect of herpesvirus-host interactions. In particular, herpesviruses display different mechanisms to modulate and usurp the most abundant mRNA modification, N6-methyladenosine or m⁶A. Some herpesviruses interfere with m⁶A methylation of transcripts, while others enhance or take advantage of m⁶A methylation of viral and/or cellular transcripts. In many cases, herpesviruses appear to modulate the m⁶A methylation process to suppress the antiviral host response. This review highlights the strategies used by members of the different herpesvirus subfamilies to manipulate host m⁶A mediators and how these contribute to virus replication and the antiviral host response. Research aimed at deciphering the interaction of herpesviruses with the m⁶A epitranscriptome not only may lead to new avenues in the design of antiviral and immunomodulatory strategies, but also provides new insights in the regulation and the role of m⁶A transcript methylation in general.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0172324"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conformational flexibility is a critical factor in designing broad-spectrum human norovirus protease inhibitors.","authors":"Son Pham, Boyang Zhao, Neetu Neetu, Banumathi Sankaran, Ketki Patil, Sasirekha Ramani, Yongcheng Song, Mary K Estes, Timothy Palzkill, B V Venkataram Prasad","doi":"10.1128/jvi.01757-24","DOIUrl":"10.1128/jvi.01757-24","url":null,"abstract":"<p><p>Human norovirus (HuNoV) is a leading cause of gastroenteritis worldwide and is associated with significant morbidity, mortality, and economic impact. There are currently no licensed antiviral drugs for the treatment of HuNoV-associated gastroenteritis. The HuNoV protease plays a critical role in the initiation of virus replication by cleaving the polyprotein. Thus, it is an ideal target for developing antiviral small-molecule inhibitors. While rupintrivir, a potent small-molecule inhibitor of several picornavirus proteases, effectively inhibits GI.1 protease, it is an order of magnitude less effective against GII protease. Other GI.1 protease inhibitors also tend to be less effective against GII proteases. To understand the structural basis for the potency difference, we determined the crystal structures of proteases of GI.1, pandemic GII.4 (Houston and Sydney), and GII.3 in complex with rupintrivir. These structures show that the open substrate pocket in GI protease binds rupintrivir without requiring significant conformational changes, whereas, in GII proteases, the closed pocket flexibly extends, reorienting arginine-112 in the BII-CII loop to accommodate rupintrivir. Structures of R112A protease mutants with rupintrivir, coupled with enzymatic and inhibition studies, suggest R112 is involved in displacing both substrate and ligands from the active site, implying a role in the release of cleaved products during polyprotein processing. Thus, the primary determinant for differential inhibitor potency between the GI and GII proteases is the increased flexibility in the BII-CII loop of the GII proteases caused by the H-G mutation in this loop. Therefore, the inherent flexibility of the BII-CII loop in GII proteases is a critical factor to consider when developing broad-spectrum inhibitors for HuNoV proteases.</p><p><strong>Importance: </strong>Human noroviruses are a significant cause of sporadic and epidemic gastroenteritis worldwide. There are no vaccines or antiviral drugs currently available to treat infections. Our work elucidates the structural differences between GI.1 and GII proteases in response to inhibitor binding and will inform the future development of broad-spectrum norovirus protease inhibitors.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0175724"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of PD-1 and CD44 in CD4⁺ T cells by circulatory extracellular vesicles from severe dengue patients drives endothelial damage via the NF-kB signaling pathway.","authors":"Sharda Kumari, Ankit Biswas, Tushar Kanti Maiti, Bhaswati Bandyopadhyay, Arup Banerjee","doi":"10.1128/jvi.01861-24","DOIUrl":"10.1128/jvi.01861-24","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) emerged as critical contributors to the pathogenesis of vascular endothelial barrier dysfunction during the inflammatory response to infection. However, the contribution of circulating EVs to modifying endothelial function during dengue virus infection remains unclear. In this study, we showed that severe dengue patients' plasma-derived EV (SD-EV) were found to carry elevated levels of different protein cargos, e.g., immunoregulatory proteins (PD-L1, CD44). Further, we demonstrated that SD-EV induces PD-1 and CD44 expression on CD4⁺ T cells. SD-EV-modulated CD4⁺ T (SD-EV-CD4) cells released secretome delayed endothelial cell (EC) migration, arrested them in the G1 phase, and augmented the expression of PD-L1 and ICAM-1 expression on EC through the Notch signaling pathway. Blocking SD-EV and CD4⁺ T-cell interaction through the PD-1/PD-L1 pathway partially rescued the CD4⁺ T cell's effect on EC but did not alter ICAM-1 expression on EC. We observed that the ICAM-1 expression on EC and hyaluronic acid (HA) release from EC was mediated by CD44, which was elevated on SD-EV-modulated CD4⁺ T cells (SD-EV-CD4), indicating a permeability defect. Blocking of CD44 on SD-EV-CD4 significantly reduced ICAM-1 expression on EC. Further, depletion of specific cytokines, e.g., TNF-α and not IFN-γ from the SD-EV-CD4 secretome, reduced ICAM-1 expression, decreased transendothelial electrical resistance, and induced apoptosis on EC significantly. Treatment with NF-kB inhibitor before secretome addition to EC reduced ICAM-1 expression on EC. In conclusion, we provided evidence that SD-EV-CD4 carrying PD-1 and CD44, when interacting with EC, significantly affected endothelial cell properties and may be significant in dengue-mediated endothelial dysfunction.IMPORTANCEExtracellular vesicles (EVs) are small membrane vesicles secreted into biological fluids, including plasma from living cells, holding insights into pathological processes. Studying EVs under pathological conditions is extremely important as they play a selective role in intercellular communication and modulation of immune response under diverse pathological conditions. However, there is less clarity on how circulatory extracellular vesicles influence immune cells during dengue virus (DV) infection and impact pathogenesis. Our present study highlights the impact of severe dengue patients' plasma-derived EV (SD-EV) on CD4⁺ T cells and together induce endothelial barrier dysfunction. We provided evidence that SD-EV induces PD-1 and CD44 on CD4⁺ T cells and, when interacting with endothelial cells (EC), drives endothelial damage through direct interaction or secretome and may be significant in dengue-mediated endothelial dysfunction.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0186124"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epithelial-to-mesenchymal transition and live cell extrusion contribute to measles virus release from human airway epithelia.","authors":"Camilla E Hippee, Lorellin A Durnell, Justin W Kaufman, Eileen Murray, Brajesh K Singh, Patrick L Sinn","doi":"10.1128/jvi.01220-24","DOIUrl":"10.1128/jvi.01220-24","url":null,"abstract":"<p><p>Measles virus (MeV) is a highly contagious respiratory virus transmitted via aerosols. To understand how MeV exits the airways of an infected host, we use unpassaged primary cultures of human airway epithelial cells (HAE). MeV typically remains cell-associated in HAE and forms foci of infection, termed infectious centers, by directly spreading cell-to-cell. We previously described the phenomenon in which infectious centers detach <i>en masse</i> from HAE and remain viable. Here, we investigate the mechanism of this cellular detachment. Via immunostaining, we observed loss of tight junction and cell adhesion proteins within infectious centers. These morphological changes indicate activation of epithelial-to-mesenchymal transition (EMT). EMT can contribute to wound healing in respiratory epithelia by mobilizing nearby cells. Inhibiting TGF-β, and thus EMT, reduced infectious center detachment. Compared with uninfected cells, MeV-infected cells also expressed increased levels of sphingosine kinase 1 (SK1), a regulator of live cell extrusion. Live cell extrusion encourages cells to detach from respiratory epithelia by contracting the actomyosin of neighboring cells. Inhibition or induction of live cell extrusion impacted infectious center detachment rates. Thus, these two related pathways contributed to infectious center detachment in HAE. Detached infectious centers contained high titers of virus that may be protected from the environment, allowing the virus to live on surfaces longer and infect more hosts.IMPORTANCEMeasles virus (MeV) is an extremely contagious respiratory pathogen that continues to cause large, disruptive outbreaks each year. Here, we examine mechanisms of detachment of MeV-infected cells. MeV spreads cell-to-cell in human airway epithelial cells (HAE) to form groups of infected cells, termed \"infectious centers\". We reported that infectious centers ultimately detach from HAE as a unit, carrying high titers of virus. Viral particles within cells may be more protected from environmental conditions, such as ultraviolet radiation and desiccation. We identified two host pathways, epithelial-to-mesenchymal transition and live cell extrusion, that contribute to infectious center detachment. Perturbing these pathways altered the kinetics of infectious center detachment. These pathways influence one another and contribute to epithelial wound healing, suggesting that infectious center detachment may be a usurped consequence of the host's response to infection that benefits MeV by increasing its transmissibility between hosts.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0122024"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction for Antonova et al., \"Genomic transfer via membrane vesicle: a strategy of giant phage phiKZ for early infection\".","authors":"Daria Antonova, Anna Nichiporenko, Mariia Sobinina, Yueqi Wang, Innokentii E Vishnyakov, Andrey Moiseenko, Inna Kurdyumova, Yuri M Chesnokov, Elizaveta Stepanchikova, Maria Bourkaltseva, Valeriya R Samygina, Mikhail Khodorkovskii, Olga S Sokolova, Maria V Yakunina","doi":"10.1128/jvi.02223-24","DOIUrl":"10.1128/jvi.02223-24","url":null,"abstract":"","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0222324"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}