首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.
Hantaviruses, similar to several emerging zoonotic viruses, persistently infect their natural reservoir hosts, without causing overt signs of disease. Spillover to incidental human hosts results in morbidity and mortality mediated by excessive proinflammatory and cellular immune responses. The mechanisms mediating the persistence of hantaviruses and the absence of clinical symptoms in rodent reservoirs are only starting to be uncovered. Recent studies indicate that during hantavirus infection, proinflammatory and antiviral responses are reduced and regulatory responses are elevated at sites of increased virus replication in rodents. The recent discovery of structural and non-structural proteins that suppress type I interferon responses in humans suggests that immune responses in rodent hosts could be mediated directly by the virus. Alternatively, several host factors, including sex steroids, glucocorticoids, and genetic factors, are reported to alter host susceptibility and may contribute to persistence of hantaviruses in rodents. Humans and reservoir hosts differ in infection outcomes and in immune responses to hantavirus infection; thus, understanding the mechanisms mediating viral persistence and the absence of disease in rodents may provide insight into the prevention and treatment of disease in humans. Consideration of the coevolutionary mechanisms mediating hantaviral persistence and rodent host survival is providing insight into the mechanisms by which zoonotic viruses have remained in the environment for millions of years and continue to be transmitted to humans.Hantaviruses are negative sense, enveloped RNA viruses (family: Bunyaviridae) that are comprised of three RNA segments, designated small (S), medium (M), and large (L), which encode the viral nucleocapsid (N), envelope glycoproteins (GN and GC), and an RNA polymerase (Pol), respectively. More than 50 hantaviruses have been found worldwide [1]. Each hantavirus appears to have coevolved with a specific rodent or insectivore host as similar phylogenetic trees are produced from virus and host mitochondrial gene sequences [2]. Spillover to humans causes hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS), depending on the virus [3][5]. Although symptoms vary, a common feature of both HFRS and HCPS is increased permeability of the vasculature and mononuclear infiltration [4]. Pathogenesis of HRFS and HCPS in humans is hypothesized to be mediated by excessive proinflammatory and CD8+ T cell responses ().

Table 1

Summary of Immune Responses in Humans during Hantavirus Infection.
Categorical ResponseImmune MarkerEffect of InfectionVirus Speciesa In Vitro/In VivoTissue or Cell Typeb, Phase of Infectionc References
Innate RIG-IElevatedSNVIn vitroHUVEC, ≤24 h p.i. [79]
ReducedNY-1VIn vitroHUVEC, ≤24 h p.i. [37]
TLR3ElevatedSNVIn vitroHUVEC, ≤24 h p.i. [79]
IFN-βElevatedPUUV, PHV, ANDVIn vitroHSVEC, HMVEC-L, ≤24 h p.i. [36],[80]
ReducedTULV, PUUV NSsIn vitroCOS-7 and MRC5 cells, ≤24 h p.i. [32],[33]
IFN-αElevatedPUUV, HTNVIn vitroMФ, DCs, 4 days p.i. [30]
No changeHTNVIn vivoBlood, acute [81]
IRF-3, IRF-7ElevatedSNV, HTNV, PHV, ANDVIn vitroHMVEC-L, ≤24 h p.i. [33],[38]
MxAElevatedHTNV, NY-1V, PHV, PUUV, ANDV, SNV, TULVIn vitroMФ,HUVEC,HMVEC-L, 6 h–4 days p.i. [36], [39][41],[79]
MHC I and IIElevatedHTNVIn vitroDCs, 4 days p.i. [30]
CD11bElevatedPUUVIn vivoBlood, acute [82]
CD40, CD80, CD86ElevatedHTNVIn vitroDCs, 4 days p.i. [30],[83]
NK cellsElevatedPUUVIn vivoBAL, acute [84]
Proinflammatory/Adhesion IL-1βElevatedSNV, HTNVIn vivoBlood, lungs, acute [85],[86]
IL-6ElevatedSNV, PUUVIn vivoBlood, lungs, acute [85],[87],[88]
TNF-αElevatedPUUV, SNV, HTNVIn vivoBlood, lungs, kidney, acute [85],[86],[88],[89]
ElevatedHTNVIn vitroDCs, 4 days p.i. [30]
CCL5ElevatedSNV, HTNVIn vitroHMVEC-L, HUVEC, 12 h–4 days p.i. [38],[39],[90]
CXCL8ElevatedPUUVIn vivoBlood, acute [82]
ElevatedPUUVIn vivoMen, blood, acute [62]
ElevatedTULV, PHV, HTNVIn vitroHUVEC, MФ, 2–4 days p.i. [39],[91]
CXCL10ElevatedSNV, HTNV, PHVIn vitroHMVEC-L,HUVEC, 3–4 days p.i. [38],[39]
ElevatedPUUVIn vivoMen, blood, acute [62]
IL-2ElevatedSNV, HTNV, PUUVIn vivoBlood, lungs, acute [82],[86]
Nitric oxideElevatedPUUVIn vivoBlood, acute [92]
GM-CSFElevatedPUUVIn vivoWomen, blood, acute [62]
ICAM, VCAMElevatedPUUVIn vivoKidney, acute [87]
ElevatedHTNV, PHVIn vitroHUVEC, 3–4 days p.i. [30],[39]
E-selectinElevatedPUUVIn vivoBlood, acute [82]
CD8+ and CD4+ T cells IFN-γElevatedHTNV, SNVIn vivoBlood, CD4+,CD8+, lungs, acute [81],[86]
CD8+ElevatedDOBV, PUUV, HTNVIn vivoBlood, BAL, acute [52],[84],[93]
Virus-specific IFN-γ+CD8+ElevatedPUUV, SNVIn vivoPBMC, acute [45],[94]
Perforin, Granzyme BElevatedPUUVIn vivoBlood, acute [95]
CD4+CD25+ “activated”ElevatedDOBV, PUUVIn vivoPBMC, acute [89],[93]
IL-4ElevatedSNVIn vivoLungs, acute [86]
Regulatory “suppressor T cells”d ReducedHTNVIn vivoBlood, acute [52]
IL-10ElevatedPUUVIn vivoBlood, acute [86]
TGF-βElevatedPUUVIn vivoKidney, acute [89]
Humoral IgM, IgG, IgA, IgEElevatedAll hantavirusesIn vivoBlood [4]
Open in a separate windowaSNV, Sin Nombre virus; NY-1V, New York-1 virus; PUUV, Puumala virus; PHV, Prospect Hill virus; ANDV, Andes virus; TULV, Tula virus; HTNV, Hantaan virus; DOBV, Dobrava virus.bHUVEC, human umbilical vascular endothelial cells; HSVEC, human saphenous vein endothelial cells; HMVEC-L, human lung microvascular endothelial cells; COS-7, African green monkey kidney fibroblasts transformed with Simian virus 40; MRC5, human fetal lung fibroblasts; MФ, macrophages; DCs, dendritic cells; BAL, bronchoalveolar lavage, PBMC, human peripheral blood mononuclear cells.cAcute infection is during symptomatic disease in patients.dSuppressor T cells likely represent cells currently referred to as regulatory T cells.

Table 2

Summary of Immune Responses in Rodents during Hantavirus Infection.
Categorical ResponseImmune MarkerEffect of InfectionVirus Speciesa Host, Tissue or Cell Typeb Phase of Infectionc References
Innate TLR7ReducedSEOVMale Norway rats, lungsAcute, Persistent [19]
ElevatedSEOVFemale Norway rats, lungsAcute, Persistent [19]
RIG-IElevatedSEOVFemale Norway rats, lungsAcute, Persistent [19]
ElevatedSEOVNewborn rats, thalamusAcute [96]
TLR3ElevatedSEOVMale Norway rats, lungsAcute, Persistent [19]
IFN-βReducedSEOVMale Norway rats, lungsAcute, Persistent [19],[61]
ElevatedSEOVFemale Norway rat lungsAcute [19],[61]
Mx2ReducedSEOVMale Norway rats, lungsAcute, Persistent [19],[60]
ElevatedSEOVFemale Norway rats, lungsAcute, Persistent [19],[60]
ElevatedHTNV, SEOVMiced, fibroblasts transfected with Mx23–4 days p.i. [97]
JAK2ElevatedSEOVFemale Norway rats, lungsAcute [60]
MHC IIElevatedPUUVBank volesGenetic susceptibility [74]
Proinflammatory/Adhesion IL-1βReducedSEOVMale Norway rats, lungsPersistent [29]
IL-6ReducedSEOVMale and female Norway rats, lungsAcute, Persistent [29],[61]
ElevatedSEOVMale rats, spleenAcute [29]
TNF-αReducedHTNVNewborn miced, CD8+, spleenAcute [49],[50]
ReducedSEOVMale Norway rats, lungsAcute, Persistent [29],[42],[61]
ElevatedSEOVFemale Norway rats, lungsPersistent [61]
CX3CL1, CXCL10ReducedSEOVMale Norway rats, lungsAcute, Persistent [29]
ElevatedSEOVMale Norway rats, spleenAcute [29]
CCL2, CCL5ElevatedSEOVMale Norway rats, spleenAcute [29]
NOS2ReducedSEOVMale Norway rats, lungsAcute, Persistent [29],[61]
ElevatedSEOVMale Norway rats, spleenAcute [29]
ElevatedHTNVMouse MФd, in vitro6 h p.i. [98]
VCAM, VEGFElevatedSEOVMale Norway rats, spleenAcute [29]
CD8+ and CD4+ T cells CD8+ReducedHTNVNewborn miced, spleenPersistent [50]
ElevatedHTNVSCID miced, CD8+ transferred, spleenPersistence [49]
ElevatedSEOVFemale Norway rats, lungsPersistent [61]
IFN-γElevatedSEOVFemale Norway rats, lungsPersistent [61]
ElevatedSEOVMale Norway rats, spleenAcute [29]
ElevatedSEOVMale and female Norway rats, splenocytesAcute [20]
ElevatedSNVDeer mice, CD4+ T cellsAcute [48]
ElevatedHTNVNewborn miced, CD8+ T cells, spleenAcute [50]
ReducedHTNVNewborn miced, CD8+ T cells, spleenPersistent [99]
IFN-γRElevatedSEOVFemale Norway rats, lungsAcute, Persistent [60]
ReducedSEOVMale Norway rats, lungsPersistent [60]
T cellsElevatedSEOVNude ratsPersistence [47]
ElevatedHTNVNude miced Persistence [100]
IL-4ReducedSEOVMale Norway rats, lungsAcute, Persistent [61]
ElevatedSNVDeer mice, CD4+ T cellsAcute [48]
ElevatedSEOVMale and female Norway rats, splenocytesAcute [20]
Regulatory Regulatory T cellsElevatedSEOVMale Norway rats, lungsPersistent [42],[61]
FoxP3ElevatedSEOVMale Norway rats, lungsPersistent [29],[42],[61]
TGF-βElevatedSEOVMale Norway rats, lungsPersistent [29]
SNVDeer mice, CD4+ T cellsPersistent [48]
IL-10ReducedSEOVMale Norway rats, lungs and spleenAcute, Persistent [29]
ElevatedSNVDeer mice, CD4+ T cellsAcute [48]
Humoral IgGElevatedSNVDeer micePersistent [12],[57]
ElevatedSEOVNorway ratsPersistent [16],[17]
ElevatedHTNVField micePersistent [15]
ElevatedPUUVBank volesPersistent [14]
ElevatedBCCVCotton ratsPersistent [18],[58]
Open in a separate windowaSEOV, Seoul virus; HTNV, Hantaan virus, PUUV, Puumala virus; SNV, Sin Nombre virus; PUUV, Puumala virus; BCCV, Black Creek Canal virus.bMФ, macrophages.cAcute infection is <30 days p.i. and persistent infection is ≥30 days p.i.d Mus musculus, non-natural reservoir host for hantaviruses.In contrast to humans, hantaviruses persistently infect their reservoir hosts, presumably causing lifelong infections [6]. Hantaviruses are shed in saliva, urine, and feces, and transmission among rodents or from rodents to humans occurs by inhalation of aerosolized virus in excrement or by transmission of virus in saliva during wounding [7],[8]. Although widely disseminated throughout the rodent host, high amounts of hantaviral RNA and antigen are consistently identified in the lungs of their rodent hosts, suggesting that the lungs may be an important site for maintenance of hantaviruses during persistent infection [9][18]. Hantavirus infection in rodents is characterized by an acute phase of peak viremia, viral shedding, and virus replication in target tissues, followed by a persistent phase of reduced, cyclical virus replication despite the presence of high antibody titers (Figure 1) [12][16], [18][20]. The onset of persistent infection varies across hantavirus–rodent systems, but generally the acute phase occurs during the first 2–3 weeks of infection and virus persistence is established thereafter (Figure 1).Open in a separate windowFigure 1Kinetics of Hantavirus Infection in Rodents.Adapted from Lee et al. [15] and others [12][14],[16],[18],[20], the kinetics of relative hantaviral load in blood (red), saliva (green), and lung tissue (blue) and antibody responses (black) during the acute and persistent phases of infection are represented. The amount of genomic viral RNA, infectious virus titer, and/or relative amount of viral antigen have been incorporated as relative hantaviral load. The antibody response is integrated as the relative amount of anti-hantavirus IgG and/or neutralizing antibody titers.Hantavirus infection alone does not cause disease, as reservoir hosts and non-natural hosts (e.g., hamsters infected with Sin Nombre virus [SNV] or Choclo virus) may support replicating virus in the absence of overt disease [12],[14],[16],[18],[21],[22]. Our primary hypothesis is that certain immune responses that are mounted in humans during hantavirus infection are suppressed in rodent reservoirs to establish and maintain viral persistence, while preventing disease (相似文献   

2.
Analysis of the morphological characters in North and South American horses present during Paleoindian time indicates that at least eight Equus ecospecies occurred in North America. In South America, Equus had radiated into four ecospecies, Hippidion had one, and Onohippidium had three geographically separate ecospecies. These species are found in archeological deposits ranging from ca. 13,000 to 8,000 yr B.P., in tropical habitats as well as in the high Andean and Patagonian colder ecotopes.  相似文献   

3.
4.
Three attributes of communities—the number, relative abundances,and phenotypic attributes of coexisting species—togetherdefine their "structure," as the term has been used in the literature.Most ecologists have tried to uncover determinants of communitystructure by analyzing patterns of morphology or resource use,or by experimentally manipulating the species composition orenvironmental context of communities. Less often used is a mechanisticanalysis of processes operating at the level of individualsor populations. I discuss the logical basis for each of these approaches andillustrate their virtues and limitations with examples drawnfrom work on heteromyid rodents. While pattern analytic andexperimental approaches have provided an efficient means ofidentifying proximate determinants of species number and relativeabundance, a mechanistic approach holds more promise for answeringquestions about the ultimate determinants of phenotypic patternswithin communities  相似文献   

5.
The three-wave migration hypothesis of Greenberg et al. has permeated the genetic literature on the peopling of the Americas. Greenberg et al. proposed that Na-Dene, Aleut-Eskimo and Amerind are language phyla which represent separate migrations from Asia to the Americas. We show that a unique allele at autosomal microsatellite locus D9S1120 is present in all sampled North and South American populations, including the Na-Dene and Aleut-Eskimo, and in related Western Beringian groups, at an average frequency of 31.7%. This allele was not observed in any sampled putative Asian source populations or in other worldwide populations. Neither selection nor admixture explains the distribution of this regionally specific marker. The simplest explanation for the ubiquity of this allele across the Americas is that the same founding population contributed a large fraction of ancestry to all modern Native American populations.  相似文献   

6.
. History of Dogs in the Early Americas. Marion Schwartz. New Haven, CT: Yale University Press, 1997. 233 pp.  相似文献   

7.
Chiefdoms and Chieftaincy in the Americas. Elsa M. Redmond. ed. Gainesville: University Press of Florida, 1998. 303 pp.  相似文献   

8.

Background

Numerous studies have demonstrated the life-extending effect of caloric restriction. It is generally accepted that caloric restriction has health benefits, such as prolonging lifespan and delaying the onset and progression of CKD in various species, especially in rodent models. Although many studies have tested the efficacy of caloric restriction, no complete quantitative analysis of the potential beneficial effects of reducing caloric intake on the development and progression of CKD has been published.

Methods

All studies regarding the relationship between caloric restriction and chronic kidney diseases were searched in electronic databases, including PubMed/MEDLINE, EMBASE, Science Citation Index (SCI), OVID evidence-based medicine, Chinese Bio-medical Literature and Chinese science and technology periodicals (CNKI, VIP, and Wan Fang). The pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated by using fixed- or random-effects models.

Results

The data from 27 of all the studies mentioned above was used in the Meta analysis. Through the meta-analysis, we found that the parameter of blood urea nitrogen, serum creatinine and urinary protein levels of the AL group was significant higher than that of the CR group, which are 4.11 mg/dl, 0.08mg/dl and 33.20mg/kg/24h, respectively. The incidence of the nephropathy in the caloric restriction (CR) group was significantly lower than that in the ad libitum—fed (AL) group. We further introduced the subgroup analysis and found that the effect of caloric restriction on the occurrence of kidney disease was only significant with prolonged intervention; the beneficial effects of CR on the 60%-caloric-restriction group were greater than on the less-than-60%-caloric-restriction group, and caloric restriction did not show obvious protective effects in genetically modified strains. Moreover, survival rate of the caloric restriction group is much higher than that of the ad libitum—fed (AL) group.

Conclusions

Our findings demonstrate for the first time that compared with the AL group, the caloric restriction indeed decreased urea nitrogen, creatinine, urine protein, incidence of kidney diseases and increased the survival rate on 700~800 days.  相似文献   

9.
10.
It has been clearly established that the Portuguese introduced coconuts to the Cape Verde islands in 1499, and these supplied the Atlantic coasts and the Caribbean in the 1500s. By contrast, early 16th century reports of coconuts on the Pacific coast of Panama are controversial. Recent DNA analysis of modern coconut populations there shows them to be similar to Philippine varieties, agreeing with morphometric analysis. Hence, coconuts must have been brought by boat from the western Pacific, but no archaeological, ethnobotanical or linguistic evidence for pre-Columbian coconuts has been found. Thus, the most parsimonious explanation is that coconuts were introduced to Panama after Spanish conquest, as supported by DNA analysis and historical records of Spanish voyages. New collections along the Pacific coast, from Mexico to Colombia, are increasing the sampling for genetic analysis, and further work in the Philippines is suggested to test probable origins. Unless new archaeological discoveries prove otherwise, the strong hypothesis of Philippine origin should direct future research on the sources of American Pacific coast coconuts.  相似文献   

11.

Background

Leishmaniasis remains a global health problem because of the substantial holes that remain in our understanding of sand fly ecology and the failure of traditional vector control methods. The specific larval food source is unknown for all but a few sand fly species, and this is particularly true for the vectors of Leishmania parasites. We provide methods and materials that could be used to understand, and ultimately break, the transmission cycle of zoonotic cutaneous leishmaniasis.

Methods and Findings

We demonstrated in laboratory studies that analysis of the stable carbon and nitrogen isotopes found naturally in plant and animal tissues was highly effective for linking adult sand flies with their larval diet, without having to locate or capture the sand fly larvae themselves. In a field trial, we also demonstrated using this technique that half of captured adult sand flies had fed as larvae on rodent feces. Through the identification of rodent feces as a sand fly larval habitat, we now know that rodent baits containing insecticides that have been shown in previous studies to pass into the rodents'' feces and kill sand fly larvae also could play a future role in sand fly control. In a second study we showed that rubidium incorporated into rodent baits could be used to demonstrate the level of bloodfeeding by sand flies on baited rodents, and that the elimination of sand flies that feed on rodents can be achieved using baits containing an insecticide that circulates in the blood of baited rodents.

Conclusions

Combined, the techniques described could help to identify larval food sources of other important vectors of the protozoa that cause visceral or dermal leishmaniasis. Unveiling aspects of the life cycles of sand flies that could be targeted with insecticides would guide future sand fly control programs for prevention of leishmaniasis.  相似文献   

12.
13.
Oecologia - Species diversity has been proposed to decrease prevalence of disease in a wide variety of host–pathogen systems, in a phenomenon labeled the dilution effect. This phenomenon was...  相似文献   

14.
15.
Craniofacial variation is investigated in Latin America and the Caribbean. The samples included in this study are two historic and one prehistoric sample from Ecuador; prehistoric and modern Cuban samples; a prehistoric Peruvian sample; two prehistoric Mexican samples and one contemporary admixed Mexican sample; a 16th/17th-century Spanish sample; and Terry blacks. Biological distance is investigated using traditional craniometrics by computing size and shape variables according to Mosimann and colleagues. This study shows that there is much biological variation within the Americas.  相似文献   

16.
17.
18.
Music education has always required advocacy to solidify its place in the school curriculum. Music teachers are increasingly called on to justify their existence and importance in the schools, and yet, are often unprepared to advocate on their own behalf without the use of advocacy materials that are created on the basis of questionable research, questionable interpretations of valid research, or materials that demean the profession. This practical advocacy crisis is created by the lack of a solid philosophical basis for music education advocacy, the profusion of questionable advocacy materials available, and the lack of lobbying at the federal and state levels for meaningful laws that give arts education true core status. In the article, the author discusses suggestions for improving advocacy methods and materials.  相似文献   

19.
20.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号