The Experts below are selected from a list of 45357 Experts worldwide ranked by ideXlab platform
Yoshihiro Kawaoka - One of the best experts on this subject based on the ideXlab platform.
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key molecular factors in hemagglutinin and pb2 contribute to efficient transmission of the 2009 h1n1 pandemic influenza Virus
Journal of Virology, 2012Co-Authors: Ying Zhang, Qianyi Zhang, Yuwei Gao, Huihui Kong, Yongping Jiang, Yuntao Guan, Xianzhu Xia, Yuelong Shu, Yoshihiro KawaokaAbstract:Animal influenza Viruses pose a clear threat to public health. Transmissibility among humans is a prerequisite for a novel influenza Virus to cause a human pandemic. A novel reassortant swine influenza Virus acquired sustained human-to-human transmissibility and caused the 2009 influenza pandemic. However, the molecular aspects of influenza Virus transmission remain poorly understood. Here, we show that an amino acid in hemagglutinin (HA) is important for the 2009 H1N1 influenza pandemic Virus (2009/H1N1) to bind to human Virus Receptors and confer respiratory droplet transmissibility in mammals. We found that the change from glutamine (Q) to arginine (R) at position 226 of HA, which causes a switch in receptor-binding preference from human α-2,6 to avian α-2,3 sialic acid, resulted in a Virus incapable of respiratory droplet transmission in guinea pigs and reduced the Virus's ability to replicate in the lungs of ferrets. The change from alanine (A) to threonine (T) at position 271 of PB2 also abolished the Virus's respiratory droplet transmission in guinea pigs, and this mutation, together with the HA Q226R mutation, abolished the Virus's respiratory droplet transmission in ferrets. Furthermore, we found that amino acid 271A of PB2 plays a key role in Virus acquisition of the mutation at position 226 of HA that confers human receptor recognition. Our results highlight the importance of both the PB2 and HA genes on the adaptation and transmission of influenza Viruses in humans and provide important insights for monitoring and evaluating the pandemic potential of field influenza Viruses.
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identification of cell surface molecules involved in dystroglycan independent lassa Virus cell entry
Journal of Virology, 2012Co-Authors: Masayuki Shimojima, Ute Stroher, Hideki Ebihara, Heinz Feldmann, Yoshihiro KawaokaAbstract:Although O-mannosylated dystroglycan is a receptor for Lassa Virus, a causative agent of Lassa fever, recent findings suggest the existence of an alternative receptor(s). Here we identified four molecules as Receptors for Lassa Virus: Axl and Tyro3, from the TAM family, and dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) and liver and lymph node sinusoidal endothelial calcium-dependent lectin (LSECtin), from the C-type lectin family. These molecules enhanced the binding of Lassa Virus to cells and mediated infection independently of dystroglycan. Axl- or Tyro3-mediated infection required intracellular signaling via the tyrosine kinase activity of Axl or Tyro3, whereas DC-SIGN- or LSECtin-mediated infection and binding were dependent on a specific carbohydrate and on ions. The identification of these four molecules as Lassa Virus Receptors advances our understanding of Lassa Virus cell entry.
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influenza Virus Receptors in the human airway
Uirusu, 2006Co-Authors: Kyoko Shinya, Yoshihiro KawaokaAbstract:Avian influenza A (H5N1) Virus infections have resulted in more than 100 human deaths; yet, human-to-human transmission is rare. We demonstrated that the epithelial cells in the upper respiratory tract of humans mainly possess sialic acid linked to galactose by alpha 2,6 linkages (SA alpha 2,6Gal), a molecule preferentially recognized by human Viruses. However, many cells in the respiratory bronchioles and alveoli possess SA alpha 2,3Gal, which is preferentially recognized by avian Viruses. These facts are consistent with the observation that H5N1 Viruses can be directly transmitted from birds to humans and cause serious lower respiratory tract damage in humans. Furthermore, this anatomical difference in receptor prevalence may explain why the spread of H5N1 Viruses among humans is limited. However, since some H5N1 Viruses isolated from humans recognize human Virus Receptors, additional changes must be required for these Viruses to acquire the ability for efficient human-to-human transmission.
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avian flu influenza Virus Receptors in the human airway
Nature, 2006Co-Authors: Kyoko Shinya, Masahito Ebina, Shinya Yamada, Masao Ono, Noriyuki Kasai, Yoshihiro KawaokaAbstract:Avian and human flu Viruses seem to target different regions of a patient's respiratory tract.
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human trachea primary epithelial cells express both sialyl α2 3 gal receptor for human parainfluenza Virus type 1 and avian influenza Viruses and sialyl α2 6 gal receptor for human influenza Viruses
Glycoconjugate Journal, 2006Co-Authors: Toshihiro Kogure, Yoshihiro Kawaoka, Takashi Suzuki, Tadanobu Takahashi, Daisei Miyamoto, Kazuya I P J Hidari, Yasuo SuzukiAbstract:We reported previously that the dominant Receptors of influenza A and B Viruses, and human and murine respiroViruses, were sialylglycoproteins and gangliosides containing monosialo-lactosamine type I-and II-residues, such as sialic acid-α2-3(6)-Galβ1-3(4)-GlcNAcβ1-. In addition, the Siaα2-3Gal linkage was predominantly recognized by avian and horse influenza Viruses, and human parainfluenza Virus type 1 (hPIV-1), whereas the Siaα2-6Gal linkage was mainly recognized by human influenza Viruses (Paulson JC in “The Receptors'' [Conn M Ed] 2, 131–219 (1985); Suzuki Y, Prog Lipid Res33, 429–57 (1994); Ito T, J Virol73, 6743–51 (2000); Suzuki Y, J Virol74, 11825–31 (2000); Suzuki T, J. Virol75, 4604–4613 (2001); Suzuki Y, Biol. Pharm. Bull. 28, 399–408 (2005)). To clarify the distribution of influenza Virus Receptors on the human bronchial epithelium cell surface, we investigated a primary culture of normal human bronchial epithelial (NHBE) cells using two types of lectin (MAA and SNA), which recognize sialyl linkages (α2-3 and α2-6), using fluorescence-activated cell-sorting analysis. The results showed that both α2-3- and α2-6-linked Sias were expressed on the surface of primary human bronchial epithelial cells. The cells infected by hPIV-1 bound to MAA, confirming that cells targeted by hPIV-1 have α2-3-linked oligosaccharides. We also compared the ability of hPIV-1 and human influenza A Virus to infect primary human bronchial epithelial cells pre-treated with Siaα2-3Gal-specific sialidase from Salmonella typhimurium. No difference was observed in the number of sialidase pre-treated and non-treated cells infected with human influenza A Virus, which binds to Siaα2-6Gal-linked oligosaccharides. By contrast, the number of cells infected with hPIV-1 decreased significantly upon sialidase treatment. Thus, cultured NHBE cells showed both α2-3-linked Sias recognized by hPIV-1 and avian influenza Virus Receptors, and α2-6-linked Sias recognized by human influenza Virus Receptors.
Patricia G Spear - One of the best experts on this subject based on the ideXlab platform.
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herpes simplex Virus Receptors and ligands for cell entry
Cellular Microbiology, 2004Co-Authors: Patricia G SpearAbstract:Summary Entry of herpes simplex Virus (HSV) into cells depends upon multiple cell surface Receptors and multiple proteins on the surface of the virion. The cell surface Receptors include heparan sulphate chains on cell surface proteoglycans, a member of the tumor necrosis factor (TNF) receptor family and two members of the immunoglobulin superfamily related to the polioVirus receptor. The HSV ligands for these Receptors are the envelope glycoproteins gB and gC for heparan sulphate and gD for the protein Receptors and specific sites in heparan sulphate generated by certain 3- O -sulfotransferases. HSV gC also binds to the C3b component of complement and can block complement-mediated neutralization of Virus. The purposes of this review are to summarize available information about these cell surface Receptors and the viral ligands, gC and gD, and to discuss roles of these viral glycoproteins in immune evasion and cellular responses as well as in viral entry. HSV and disease The most common manifestations of HSV infection are mucocutaneous lesions, commonly called cold sores or fever blisters if they occur on or near the lips. Such lesions can occur anywhere that the Virus is inoculated, however. Lesions on the fingers (herpes whitlow) used to be an occupational hazard for dentists before the widespread use of surgical gloves. Herpes genitalis refers to the lesions on genitalia in sexually transmitted forms of disease. In addition, the cornea of the eye can be infected to cause keratitis. These lesions usually resolve without scarring and would not be a serious concern except that they can recur frequently. The Virus enters sensory and autonomic neurons whose axons extend to the locale of the lesions and the Virus sets up latent infections from which it can periodically be reactivated. Reactivated Virus is transported back to the body surface to cause recurrent lesions. Occasionally the Virus can also be transported to the central nervous system to cause encephalitis. Fortunately, this occurs rarely but, unfortunately, the factors that predispose to encephalitis are not known. Age must be one such factor because HSV infections in newborn infants can result in severe disseminated disease including neurological involvement. Two of the most important cellular targets in HSV disease are epithelial cells of skin and mucosa and neurons. Lymphocytes and other leucocytes can also be infected, a phenomenon of unknown significance with respect to the effectiveness of immune responses. Usually, spread of infection is by cell-to-cell contact, not via a hematagenous or lymphatic route. Some consideration will be given here to the requirements for viral entry into leucocytes, epithelial cells and neurons. There are two serotypes of HSV, HSV-1 and HSV-2. Lesions caused by HSV-1 strains cannot be distinguished from those caused by HSV-2 but there are distinct genetic and biological differences between members of the two serotypes. For example, although both HSV-1 and HSV-2 can infect either oral or genital sites, HSV-1 is more likely to reactivate frequently from oral sites and HSV-2 is more likely to reactivate from genital sites (Lafferty et al ., 1987).
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herpes simplex Virus Receptors and ligands for cell entry
Cellular Microbiology, 2004Co-Authors: Patricia G SpearAbstract:Entry of herpes simplex Virus (HSV) into cells depends upon multiple cell surface Receptors and multiple proteins on the surface of the virion. The cell surface Receptors include heparan sulphate chains on cell surface proteoglycans, a member of the tumor necrosis factor (TNF) receptor family and two members of the immunoglobulin superfamily related to the polioVirus receptor. The HSV ligands for these Receptors are the envelope glycoproteins gB and gC for heparan sulphate and gD for the protein Receptors and specific sites in heparan sulphate generated by certain 3-O-sulfotransferases. HSV gC also binds to the C3b component of complement and can block complement-mediated neutralization of Virus. The purposes of this review are to summarize available information about these cell surface Receptors and the viral ligands, gC and gD, and to discuss roles of these viral glycoproteins in immune evasion and cellular responses as well as in viral entry.
Seppo Meri - One of the best experts on this subject based on the ideXlab platform.
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autoantibodies against ganglioside gm3 are associated with narcolepsy cataplexy developing after pandemrix vaccination against 2009 pandemic h1n1 type influenza Virus
Journal of Autoimmunity, 2015Co-Authors: Annahelena Saariaho, Arja Vuorela, Tobias L Freitag, Fabio Pizza, Giuseppe Plazzi, Markku Partinen, Outi Vaarala, Seppo MeriAbstract:Abstract Following the mass vaccinations against pandemic influenza A/H1N1 Virus in 2009, a sudden increase in juvenile onset narcolepsy with cataplexy (NC) was detected in several European countries where AS03-adjuvanted Pandemrix vaccine had been used. NC is a chronic neurological disorder characterized by excessive daytime sleepiness and cataplexy. In human NC, the hypocretin-producing neurons in the hypothalamus or the hypocretin signaling pathway are destroyed by an autoimmune reaction. Both genetic (e.g. HLA-DQB1*0602) and environmental risk factors (e.g. Pandemrix) contribute to the disease development, but the underlying and the mediating immunological mechanisms are largely unknown. Influenza Virus hemagglutinin is known to bind gangliosides, which serve as host cell Virus Receptors. Anti-ganglioside antibodies have previously been linked to various neurological disorders, like the Guillain-Barre syndrome which may develop after infection or vaccination. Because of these links we screened sera of NC patients and controls for IgG anti-ganglioside antibodies against 11 human brain gangliosides (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b) and a sulfatide by using a line blot assay. Samples from 173 children and adolescents were analyzed: 48 with Pandemrix-associated NC, 20 with NC without Pandemrix association, 57 Pandemrix-vaccinated and 48 unvaccinated healthy children. We found that patients with Pandemrix-associated NC had more frequently (14.6%) anti-GM3 antibodies than vaccinated healthy controls (3.5%) ( P = 0.047). Anti-GM3 antibodies were significantly associated with HLA-DQB1*0602 ( P = 0.016) both in vaccinated NC patients and controls. In general, anti-ganglioside antibodies were more frequent in vaccinated (18.1%) than in unvaccinated (7.3%) individuals ( P = 0.035). Our data suggest that autoimmunity against GM3 is a feature of Pandemrix-associated NC and that autoantibodies against gangliosides were induced by Pandemrix vaccination.
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autoantibodies against ganglioside gm3 are associated with narcolepsy cataplexy developing after pandemrix vaccination against 2009 pandemic h1n1 type influenza Virus
Journal of Autoimmunity, 2015Co-Authors: Annahelena Saariaho, Arja Vuorela, Tobias L Freitag, Fabio Pizza, Giuseppe Plazzi, Markku Partinen, Outi Vaarala, Seppo MeriAbstract:Following the mass vaccinations against pandemic influenza A/H1N1 Virus in 2009, a sudden increase in juvenile onset narcolepsy with cataplexy (NC) was detected in several European countries where AS03-adjuvanted Pandemrix vaccine had been used. NC is a chronic neurological disorder characterized by excessive daytime sleepiness and cataplexy. In human NC, the hypocretin-producing neurons in the hypothalamus or the hypocretin signaling pathway are destroyed by an autoimmune reaction. Both genetic (e.g. HLA-DQB1*0602) and environmental risk factors (e.g. Pandemrix) contribute to the disease development, but the underlying and the mediating immunological mechanisms are largely unknown. Influenza Virus hemagglutinin is known to bind gangliosides, which serve as host cell Virus Receptors. Anti-ganglioside antibodies have previously been linked to various neurological disorders, like the Guillain-Barre syndrome which may develop after infection or vaccination. Because of these links we screened sera of NC patients and controls for IgG anti-ganglioside antibodies against 11 human brain gangliosides (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b) and a sulfatide by using a line blot assay. Samples from 173 children and adolescents were analyzed: 48 with Pandemrix-associated NC, 20 with NC without Pandemrix association, 57 Pandemrix-vaccinated and 48 unvaccinated healthy children. We found that patients with Pandemrix-associated NC had more frequently (14.6%) anti-GM3 antibodies than vaccinated healthy controls (3.5%) (P = 0.047). Anti-GM3 antibodies were significantly associated with HLA-DQB1*0602 (P = 0.016) both in vaccinated NC patients and controls. In general, anti-ganglioside antibodies were more frequent in vaccinated (18.1%) than in unvaccinated (7.3%) individuals (P = 0.035). Our data suggest that autoimmunity against GM3 is a feature of Pandemrix-associated NC and that autoantibodies against gangliosides were induced by Pandemrix vaccination.
Zheng Zhang - One of the best experts on this subject based on the ideXlab platform.
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prediction of the receptorome for the human infecting virome
Virologica Sinica, 2020Co-Authors: Zheng Zhang, Taijiao Jiang, Yousong PengAbstract:The Virus Receptors are key for the viral infection of host cells. Identification of the Virus Receptors is still challenging at present. Our previous study has shown that human Virus receptor proteins have some unique features including high N-glycosylation level, high number of interaction partners and high expression level. Here, a random-forest model was built to identify human Virus receptorome from human cell membrane proteins with an accepted accuracy based on the combination of the unique features of human Virus Receptors and protein sequences. A total of 1424 human cell membrane proteins were predicted to constitute the receptorome of the human-infecting virome. In addition, the combination of the random-forest model with protein-protein interactions between human and Viruses predicted in previous studies enabled further prediction of the Receptors for 693 human-infecting Viruses, such as the enteroVirus, noroVirus and West Nile Virus. Finally, the candidate alternative Receptors of the SARS-CoV-2 were also predicted in this study. As far as we know, this study is the first attempt to predict the receptorome for the human-infecting virome and would greatly facilitate the identification of the Receptors for Viruses.
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single cell rna sequencing of 13 human tissues identify cell types and Receptors of human coronaViruses
Biochemical and Biophysical Research Communications, 2020Co-Authors: Furong Qi, Shen Qian, Shuye Zhang, Zheng ZhangAbstract:The new coronaVirus (SARS-CoV-2) outbreak from December 2019 in Wuhan, Hubei, China, has been declared a global public health emergency. Angiotensin I converting enzyme 2 (ACE2), is the host receptor by SARS-CoV-2 to infect human cells. Although ACE2 is reported to be expressed in lung, liver, stomach, ileum, kidney and colon, its expressing levels are rather low, especially in the lung. SARS-CoV-2 may use co-Receptors/auxiliary proteins as ACE2 partner to facilitate the Virus entry. To identify the potential candidates, we explored the single cell gene expression atlas including 119 cell types of 13 human tissues and analyzed the single cell co-expression spectrum of 51 reported RNA Virus Receptors and 400 other membrane proteins. Consistent with other recent reports, we confirmed that ACE2 was mainly expressed in lung AT2, liver cholangiocyte, colon colonocytes, esophagus keratinocytes, ileum ECs, rectum ECs, stomach epithelial cells, and kidney proximal tubules. Intriguingly, we found that the candidate co-Receptors, manifesting the most similar expression patterns with ACE2 across 13 human tissues, are all peptidases, including ANPEP, DPP4 and ENPEP. Among them, ANPEP and DPP4 are the known Receptors for human CoVs, suggesting ENPEP as another potential receptor for human CoVs. We also conducted "CellPhoneDB" analysis to understand the cell crosstalk between CoV-targets and their surrounding cells across different tissues. We found that macrophages frequently communicate with the CoVs targets through chemokine and phagocytosis signaling, highlighting the importance of tissue macrophages in immune defense and immune pathogenesis.
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prediction of the receptorome for the human infecting virome
bioRxiv, 2020Co-Authors: Zheng Zhang, Taijiao Jiang, Yousong PengAbstract:Abstract The Virus Receptors are key for the viral infection of host cells. Identification of the Virus Receptors is still challenging at present. Our previous study has shown that human Virus receptor proteins have some unique features including high N-glycosylation level, high number of interaction partners and high expression level. Here, a random-forest model was built to identify human Virus receptorome from human cell membrane proteins with an accepted accuracy based on the combination of the unique features of human Virus Receptors and protein sequences. A total of 1380 human cell membrane proteins were predicted to constitute the receptorome of the human-infecting virome. In addition, the combination of the random-forest model with protein-protein interactions between human and Viruses predicted in previous studies enabled further prediction of the Receptors for 693 human-infecting Viruses, such as the EnteroVirus, NoroVirus and West Nile Virus. As far as we know, this study is the first attempt to predict the receptorome for the human-infecting virome and would greatly facilitate the identification of the Receptors for Viruses.
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prediction of receptorome for human infecting virome
bioRxiv, 2020Co-Authors: Zheng Zhang, Taijiao Jiang, Yousong PengAbstract:The Virus receptor is key for viral infection of host cells. Identification of the Virus receptor is still challenging at present. Our previous study has shown that human Virus receptor proteins have some unique features including high level of N-glycosylation, high number of interaction partners and high expressions. Here, we built a random-forest model to identify human Virus receptorome from human cell membrane proteins with accepted accuracy based on combination of unique features of human Virus Receptors and protein sequences. A total of 729 human cell membrane proteins were predicted to constitute the receptorome for the human-infecting virome. Combination of the random-forest model with protein-protein interactions between human and Viruses predicted in previous studies further predicted Receptors for 693 human-infecting Viruses, such as the EnteroVirus, NoroVirus and West Nile Virus. Finally, we predicted the candidate alternative Receptors for the 2019-nCoV. The study would greatly facilitate identification of Receptors for human-infecting virome.
Joseph Stanek - One of the best experts on this subject based on the ideXlab platform.
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neuroblastomas vary widely in their sensitivities to herpes simplex virotherapy unrelated to Virus Receptors and susceptibility
Gene Therapy, 2016Co-Authors: Py Wang, H M Swain, A L Kunkler, Cy Chen, Brian Hutzen, Michael A Arnold, Keri A Streby, Margaret H Collins, B Dipasquale, Joseph StanekAbstract:Although most high-risk neuroblastomas are responsive to chemotherapy, relapse is common and long-term survival is less than 40%, underscoring the need for more effective treatments. We evaluated the responsiveness of 12 neuroblastoma cell lines to the Δγ134.5 attenuated oncolytic HSV, Seprehvir (HSV1716), which is currently used in pediatric phase I trials. We found that entry of Seprehvir in neuroblastoma cells is independent of the expression of nectin-1 and the sum of all four known major HSV entry Receptors. We observed varying levels of sensitivity and permissivity to Seprehvir, suggesting that the cellular anti-viral response, not Virus entry, is the key determinant of efficacy with this Virus. In vivo, we found significant anti-tumor efficacy following Seprehvir treatment, which ranged from 6/10 complete responses in the CHP-134 model to a mild prolonged median survival in the SK-N-AS model. Taken together, these data suggest that anti-tumor efficacy cannot be solely predicted based on in vitro response. Whether or not this discordance holds true for other Viruses or tumor types is unknown. Our results also suggest that profiling the expression of known viral entry Receptors on neuroblastoma cells may not be entirely predictive of their susceptibility to Seprehvir therapy.
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neuroblastomas vary widely in their sensitivities to herpes simplex virotherapy unrelated to Virus Receptors and susceptibility
Gene Therapy, 2016Co-Authors: Py Wang, H M Swain, A L Kunkler, Cy Chen, Brian Hutzen, Michael A Arnold, Keri A Streby, Margaret H Collins, B Dipasquale, Joseph StanekAbstract:Although most high-risk neuroblastomas are responsive to chemotherapy, relapse is common and long-term survival is < 40%, underscoring the need for more effective treatments. We evaluated the responsiveness of 12 neuroblastoma cell lines to the Δγ134.5 attenuated oncolytic herpes simplex Virus (oHSV), Seprehvir (HSV1716), which is currently used in pediatric phase I trials. We found that entry of Seprehvir in neuroblastoma cells is independent of the expression of nectin-1 and the sum of all four known major HSV entry Receptors. We observed varying levels of sensitivity and permissivity to Seprehvir, suggesting that the cellular anti-viral response, not Virus entry, is the key determinant of efficacy with this Virus. In vivo, we found significant anti-tumor efficacy following Seprehvir treatment, which ranged from 6/10 complete responses in the CHP-134 model to a mild prolonged median survival in the SK-N-AS model. Taken together, these data suggest that anti-tumor efficacy cannot be solely predicted based on in vitro response. Whether or not this discordance holds true for other Viruses or tumor types is unknown. Our results also suggest that profiling the expression of known viral entry Receptors on neuroblastoma cells may not be entirely predictive of their susceptibility to Seprehvir therapy.
