TO THE EDITOR We read the study by Medeiros-Filho et al with much interest. The study shed light on early HCV RNA kinetics in conjunction with liver cirrhosis, different genotypes （gen-1 vs gen-3） of HCV and sustain...TO THE EDITOR We read the study by Medeiros-Filho et al with much interest. The study shed light on early HCV RNA kinetics in conjunction with liver cirrhosis, different genotypes （gen-1 vs gen-3） of HCV and sustained viral response （SVR） rates. In particular, Medeiros-Filho et al showed that the HCV RNA first phase decline, under interferon-or （IFN） and ribavirin therapy,展开更多
The recent mpox outbreak(in 2022e2023)has different clinical and epidemiological features compared with previous outbreaks of the disease.During this outbreak,sexual contact was believed to be the primary transmission...The recent mpox outbreak(in 2022e2023)has different clinical and epidemiological features compared with previous outbreaks of the disease.During this outbreak,sexual contact was believed to be the primary transmission route of the disease.In addition,the community of men having sex with men(MSM)was disproportionately affected by the outbreak.This population is also disproportionately affected by HIV infection.Given that both diseases can be transmitted sexually,the endemicity of HIV,and the high sexual behavior associated with the MSM community,it is essential to understand the effect of the two diseases spreading simultaneously in an MSM population.Particularly,we aim to understand the potential effects of HIV on an mpox outbreak in the MSM population.We develop a mechanistic mathematical model of HIV and mpox co-infection.Our model incorporates the dynamics of both diseases and considers HIV treatment with antiretroviral therapy(ART).In addition,we consider a potential scenario where HIV infection increases susceptibility to mpox,and investigate the potential impact of this mechanism on mpox dynamics.Our analysis shows that HIV can facilitate the spread of mpox in an MSM population,and that HIV treatment with ART may not be sufficient to control the spread of mpox in the population.However,we showed that a moderate use of condoms or reduction in sexual contact in the population combined with ART is beneficial in controlling mpox transmission.Based on our analysis,it is evident that effective control of HIV,specifically through substantial ART use,moderate condom compliance,and reduction in sexual contact,is imperative for curtailing the transmission of mpox in an MSM population and mitigating the compounding impact of these intertwined epidemics.展开更多
In this paper we study influenza viral membrane deformation related to the refolding of Hemagglutinin(HA)protein.The focus of the paper is to understand membrane deformation and budding due to experimentally observed ...In this paper we study influenza viral membrane deformation related to the refolding of Hemagglutinin(HA)protein.The focus of the paper is to understand membrane deformation and budding due to experimentally observed linear HA-protein clusters,which have not been mathematically studied before.The viral membrane is modeled as a two dimensional incompressible lipid bilayer with bending rigidity.For tensionless membranes,we derive an analytical solution while for membrane under tension we solve the problem numerically.Our solution for tensionless membranes shows that the height of membrane deformation increases monotonically with the bending moment exerted by HA-proteins and attains its maximum when the size of the protein cluster reaches a critical value.Our results also show that the hypothesis of dimple formation proposed in the literature is valid in the two dimensional setting.Our comparative study of axisymmetric HA-clusters and linear HA-clusters reveals that the linear HA-clusters are not favorable to provide a sufficient energy required to overcome an energy barrier for a successful fusion,despite their capability to cause membrane deformation and budding.展开更多
Microscopic level interaction between fusion-peptides and lipid bilayer membranes plays a crucial role in membrane fusion,a key step of viral infection.In this paper,we use coarse-grained molecular dynamics(CGMD)simul...Microscopic level interaction between fusion-peptides and lipid bilayer membranes plays a crucial role in membrane fusion,a key step of viral infection.In this paper,we use coarse-grained molecular dynamics(CGMD)simulations to study the interaction between hemagglutinin fusion-peptides and phospholipid bilayer membranes.With CGMD,we are able to simulate the interaction of fusion peptides with a relatively large piece of membrane for a sufficiently long time period,which is necessary for a detailed understanding of the fusion process.A conformation of the peptide with a kink at the level of phosphate group is obtained,consistent with NMR and EPR studies.Our results show that the N-terminal segment of the peptide inserts more deeply into the membrane bilayer compared to the C-terminal segment,as observed in previous experiments.Our simulations also show that the presence of fusion peptides inside the membrane may cause bilayer thinning and lipid molecule disorder.Finally,our results reveal that peptides tend to aggregate,indicating cluster formation as seen in many experiments.展开更多
Background Vector-borne diseases(VBDs)are important contributors to the global burden of infectious diseases due to their epidemic potential,which can result in signifcant population and economic impacts.Oropouche fev...Background Vector-borne diseases(VBDs)are important contributors to the global burden of infectious diseases due to their epidemic potential,which can result in signifcant population and economic impacts.Oropouche fever,caused by Oropouche virus(OROV),is an understudied zoonotic VBD febrile illness reported in Central and South America.The epidemic potential and areas of likely OROV spread remain unexplored,limiting capacities to improve epidemiological surveillance.Methods To better understand the capacity for spread of OROV,we developed spatial epidemiology models using human outbreaks as OROV transmission-locality data,coupled with high-resolution satellite-derived vegetation phe‑nology.Data were integrated using hypervolume modeling to infer likely areas of OROV transmission and emergence across the Americas.Results Models based on one-support vector machine hypervolumes consistently predicted risk areas for OROV transmission across the tropics of Latin America despite the inclusion of diferent parameters such as diferent study areas and environmental predictors.Models estimate that up to 5 million people are at risk of exposure to OROV.Nevertheless,the limited epidemiological data available generates uncertainty in projections.For example,some out‑breaks have occurred under climatic conditions outside those where most transmission events occur.The distribu‑tion models also revealed that landscape variation,expressed as vegetation loss,is linked to OROV outbreaks.Conclusions Hotspots of OROV transmission risk were detected along the tropics of South America.Vegetation loss might be a driver of Oropouche fever emergence.Modeling based on hypervolumes in spatial epidemiology might be considered an exploratory tool for analyzing data-limited emerging infectious diseases for which little understand‑ing exists on their sylvatic cycles.OROV transmission risk maps can be used to improve surveillance,investigate OROV ecology and epidemiology,and inform early detection.展开更多
基金NIH grants RR06555 and P20-RR18754the U.S.Department of Energy under contract DE-AC52-06NA25396
文摘TO THE EDITOR We read the study by Medeiros-Filho et al with much interest. The study shed light on early HCV RNA kinetics in conjunction with liver cirrhosis, different genotypes （gen-1 vs gen-3） of HCV and sustained viral response （SVR） rates. In particular, Medeiros-Filho et al showed that the HCV RNA first phase decline, under interferon-or （IFN） and ribavirin therapy,
基金funded by the Canadian Institute for Health Research(CIHR)under the Mpox and other zoonotic threats Team Grant(FRN.187246)financial support from the NSERC Discovery Grant(Appl No.:RGPIN-2023-05100)+2 种基金support from IDRC(Grant No.109981)support from NSERC Discovery Grant(Grant No.RGPIN-2022-04559),NSERC Discovery Launch Supplement(Grant No:DGECR-2022-00454)New Frontier in Research Fund-Exploratory(Grant No.NFRFE-2021-00879).
文摘The recent mpox outbreak(in 2022e2023)has different clinical and epidemiological features compared with previous outbreaks of the disease.During this outbreak,sexual contact was believed to be the primary transmission route of the disease.In addition,the community of men having sex with men(MSM)was disproportionately affected by the outbreak.This population is also disproportionately affected by HIV infection.Given that both diseases can be transmitted sexually,the endemicity of HIV,and the high sexual behavior associated with the MSM community,it is essential to understand the effect of the two diseases spreading simultaneously in an MSM population.Particularly,we aim to understand the potential effects of HIV on an mpox outbreak in the MSM population.We develop a mechanistic mathematical model of HIV and mpox co-infection.Our model incorporates the dynamics of both diseases and considers HIV treatment with antiretroviral therapy(ART).In addition,we consider a potential scenario where HIV infection increases susceptibility to mpox,and investigate the potential impact of this mechanism on mpox dynamics.Our analysis shows that HIV can facilitate the spread of mpox in an MSM population,and that HIV treatment with ART may not be sufficient to control the spread of mpox in the population.However,we showed that a moderate use of condoms or reduction in sexual contact in the population combined with ART is beneficial in controlling mpox transmission.Based on our analysis,it is evident that effective control of HIV,specifically through substantial ART use,moderate condom compliance,and reduction in sexual contact,is imperative for curtailing the transmission of mpox in an MSM population and mitigating the compounding impact of these intertwined epidemics.
基金supported by the Susan Mann Dissertation Scholarship Award of York University,Canadathe Natural Science and Engineering Research Council(NSERC)of CanadaMathematics for Information Technology and Complex System(MITACS)of Canada.
文摘In this paper we study influenza viral membrane deformation related to the refolding of Hemagglutinin(HA)protein.The focus of the paper is to understand membrane deformation and budding due to experimentally observed linear HA-protein clusters,which have not been mathematically studied before.The viral membrane is modeled as a two dimensional incompressible lipid bilayer with bending rigidity.For tensionless membranes,we derive an analytical solution while for membrane under tension we solve the problem numerically.Our solution for tensionless membranes shows that the height of membrane deformation increases monotonically with the bending moment exerted by HA-proteins and attains its maximum when the size of the protein cluster reaches a critical value.Our results also show that the hypothesis of dimple formation proposed in the literature is valid in the two dimensional setting.Our comparative study of axisymmetric HA-clusters and linear HA-clusters reveals that the linear HA-clusters are not favorable to provide a sufficient energy required to overcome an energy barrier for a successful fusion,despite their capability to cause membrane deformation and budding.
基金supported by the Susan Mann Dissertation Scholarship Award of York UniversityNatural Science and Engineering Research Council(NSERC)of Canada+1 种基金Mathematics for Information Technology and Complex System(MITACS)of CanadaResearch and Development of the Next-Generation Integrated Simulation of Living Matter,a part of the Development and Use of the Next-Generation Supercomputer Project of the Ministry of Education,Culture,Sports,Science and Technology(MEXT),Japan.
文摘Microscopic level interaction between fusion-peptides and lipid bilayer membranes plays a crucial role in membrane fusion,a key step of viral infection.In this paper,we use coarse-grained molecular dynamics(CGMD)simulations to study the interaction between hemagglutinin fusion-peptides and phospholipid bilayer membranes.With CGMD,we are able to simulate the interaction of fusion peptides with a relatively large piece of membrane for a sufficiently long time period,which is necessary for a detailed understanding of the fusion process.A conformation of the peptide with a kink at the level of phosphate group is obtained,consistent with NMR and EPR studies.Our results show that the N-terminal segment of the peptide inserts more deeply into the membrane bilayer compared to the C-terminal segment,as observed in previous experiments.Our simulations also show that the presence of fusion peptides inside the membrane may cause bilayer thinning and lipid molecule disorder.Finally,our results reveal that peptides tend to aggregate,indicating cluster formation as seen in many experiments.
文摘Background Vector-borne diseases(VBDs)are important contributors to the global burden of infectious diseases due to their epidemic potential,which can result in signifcant population and economic impacts.Oropouche fever,caused by Oropouche virus(OROV),is an understudied zoonotic VBD febrile illness reported in Central and South America.The epidemic potential and areas of likely OROV spread remain unexplored,limiting capacities to improve epidemiological surveillance.Methods To better understand the capacity for spread of OROV,we developed spatial epidemiology models using human outbreaks as OROV transmission-locality data,coupled with high-resolution satellite-derived vegetation phe‑nology.Data were integrated using hypervolume modeling to infer likely areas of OROV transmission and emergence across the Americas.Results Models based on one-support vector machine hypervolumes consistently predicted risk areas for OROV transmission across the tropics of Latin America despite the inclusion of diferent parameters such as diferent study areas and environmental predictors.Models estimate that up to 5 million people are at risk of exposure to OROV.Nevertheless,the limited epidemiological data available generates uncertainty in projections.For example,some out‑breaks have occurred under climatic conditions outside those where most transmission events occur.The distribu‑tion models also revealed that landscape variation,expressed as vegetation loss,is linked to OROV outbreaks.Conclusions Hotspots of OROV transmission risk were detected along the tropics of South America.Vegetation loss might be a driver of Oropouche fever emergence.Modeling based on hypervolumes in spatial epidemiology might be considered an exploratory tool for analyzing data-limited emerging infectious diseases for which little understand‑ing exists on their sylvatic cycles.OROV transmission risk maps can be used to improve surveillance,investigate OROV ecology and epidemiology,and inform early detection.
