Reservoir host immune responses to emerging zoonotic viruses.
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ABSTRACT:
SUBMITTER: Mandl JN
PROVIDER: S-EPMC4390999 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Progress in combatting zoonoses that emerge from wildlife is often constrained by limited knowledge of the biology of pathogens within reservoir hosts. We focus on the host-pathogen dynamics of four emerging viruses associated with bats: Hendra, Nipah, Ebola, and Marburg viruses. Spillover of bat infections to humans and domestic animals often coincides with pulses of viral excretion within bat populations, but the mechanisms driving such pulses are unclear. Three hypotheses dominate current research on these emerging bat infections. First, pulses of viral excretion could reflect seasonal epidemic cycles driven by natural variations in population densities and contact rates among hosts. If lifelong immunity follows recovery, viruses may disappear locally but persist globally through migration; in either case, new outbreaks occur once births replenish the susceptible pool. Second, epidemic cycles could be the result of waning immunity within bats, allowing local circulation of viruses through oscillating herd immunity. Third, pulses could be generated by episodic shedding from persistently infected bats through a combination of physiological and ecological factors. The three scenarios can yield similar patterns in epidemiological surveys, but strategies to predict or manage spillover risk resulting from each scenario will be different. We outline an agenda for research on viruses emerging from bats that would allow for differentiation among the scenarios and inform development of evidence-based interventions to limit threats to human and animal health. These concepts and methods are applicable to a wide range of pathogens that affect humans, domestic animals, and wildlife.
| S-EPMC4973921 | biostudies-literature
Project description:Most human infectious diseases, especially recently emerging pathogens, originate from animals, and ongoing disease transmission from animals to people presents a significant global health burden. Recognition of the epidemiologic circumstances involved in zoonotic spillover, amplification, and spread of diseases is essential for prioritizing surveillance and predicting future disease emergence risk. We examine the animal hosts and transmission mechanisms involved in spillover of zoonotic viruses to date, and discover that viruses with high host plasticity (i.e. taxonomically and ecologically diverse host range) were more likely to amplify viral spillover by secondary human-to-human transmission and have broader geographic spread. Viruses transmitted to humans during practices that facilitate mixing of diverse animal species had significantly higher host plasticity. Our findings suggest that animal-to-human spillover of new viruses that are capable of infecting diverse host species signal emerging disease events with higher pandemic potential in that these viruses are more likely to amplify by human-to-human transmission with spread on a global scale.
| S-EPMC4595845 | biostudies-other
Project description:BACKGROUND:Currently, an in vitro immunogenicity screening system for the immunological assessment of potential porcine reproductive and respiratory syndrome virus (PRRSV) vaccine candidates is highly desired. Thus, in the present study, two genetically divergent PRRSVs were characterized in vitro and in vivo to identify an in vitro system and immunological markers that predict the host immune response. Porcine alveolar macrophages (PAMs) and peripheral blood mononuclear cells (PBMCs) collected from PRRSV-negative pigs were used for in vitro immunological evaluation, and the response of these cells to VR2332c or JA142c were compared with those elicited in pigs challenged with the same viruses. RESULTS:Compared with VR2332c or mock infection, JA142c induced increased levels of type I interferons and pro-inflammatory cytokines (TNF-?, IL-1?/?, IL-6, IL-8, and IL-12) in PAMs, and these elevated levels were comparable to the cytokine induction observed in PRRSV-challenged pigs. Furthermore, significantly greater numbers of activated CD4+ T cells, type I helper T cells, cytotoxic T cells and total IFN-?+ cells were observed in JA142c-challenged pigs than in VR2332c- or mock-challenged pigs. CONCLUSIONS:Based on these results, the innate immune response patterns (particularly IFN-?, TNF-? and IL-12) to specific PRRSV strains in PAMs might reflect those elicited by the same viruses in pigs.
| S-EPMC6278023 | biostudies-literature
Project description:Though previous studies have identified two strains of duck-origin Newcastle disease virus (NDV) with varying levels of pathogenicity, the relationship between the early-phase host innate immune response, and pathogenesis of ducks infected with these strains in the lungs and thymuses remains unclear. In this study, we compared the viral distribution and mRNA expression of immune-related genes in ducks following infection with two NDV strains, Duck/CH/GD/SS/10 (SS-10) and Duck/CH/GD/NH/10 (NH-10). Both NDV strains replicated systemically in tested tissues (i.e., small intestine, cecal tonsils, brain, lung, bursa of Fabricius, thymus, and spleen) and exhibited different biological properties in duck pathogenicity. Real-time quantitative polymerase chain reaction showed that the expression of TLR3, TLR7, RIG-I, MDA5, IL-1?, IL-2, IL-6, IL-8, IFN-alpha, IFN-beta, IFN-gamma in the lungs was significantly greater than in the respective thymus genes during the early post infection stage. However, in the lungs, the expression of TLR3, TLR7, IL-1?, IL-2, IL-8, IFN-alpha, IFN-gamma, and MHC II induced by SS-10 at 72 h post-inoculation (hpi) was less than with NH-10. Furthermore, the expression of IL-6 and IFN-beta in the lungs and thymuses following infection with SS-10 was greater than that with NH-10 at 24 and 48 hpi. These results highlight important differences in host innate immune responses, courses of infection, and pathogenesis following NDV infection. Further studies should work to expand understandings of the molecular mechanisms related to NDV infection.
| S-EPMC4646970 | biostudies-literature
Project description:Pathogens face a hostile and often novel environment when infecting a new host, and adaptation is likely to be an important determinant of the success in colonization and establishment. We hypothesized that resistant hosts will impose stronger selection on pathogens than susceptible hosts, which should accelerate pathogen evolution through selection biased toward effector genes. To test this hypothesis, we conducted an experimental evolution study on Xanthomonas citri subsp. citri (Xcc) in a susceptible plant species and a resistant plant species. We performed 55 rounds of repeated reinoculation of Xcc through susceptible host grapefruit (isolates G1, G2, G3) and resistant host kumquat (isolates K1, K2, K3). Consequently, only K1 and K3 isolates lost their ability to elicit a hypersensitive response (HR) in kumquat. Illumina sequencing of the parental and descendant strains P, G1, G2, G3, K1, K2 and K3 revealed that fixed mutations were biased toward type three secretion system effectors in isolates K1 and K3. Parallel evolution was observed in the K1 and K3 strains, suggesting that the mutations result from selection rather than by random drift. Our results support our hypothesis and suggest that repeated infection of resistant hosts by pathogens should be prevented to avoid selecting for adaptive pathogens.
| S-EPMC3930326 | biostudies-other
Project description:Hantaviruses are zoonotic pathogens that maintain a persistent infection in their reservoir hosts, yet the mechanisms mediating persistence remain unknown. Regulatory T cell responses cause persistent infection by suppressing proinflammatory and effector T cell activity; hantaviruses may exploit these responses to cause persistence. To test this hypothesis, male Norway rats were inoculated with Seoul virus and regulatory T cells were monitored during infection. Increased numbers of CD4(+)CD25(+)Forkhead box P3(+) T cells and expression of Forkhead box P3 and TGF-beta were observed in the lungs of male rats during persistent Seoul virus infection. To determine whether regulatory T cells modulate Seoul virus persistence, regulatory T cells were inactivated in male rats by using an anti-rat CD25 monoclonal antibody (NDS-63). Inactivation of regulatory T cells reduced the amount of Seoul virus RNA present in the lungs and the proportion of animals shedding viral RNA in saliva. Because regulatory T cells suppress proinflammatory-induced pathogenesis, pathologic observations in the lungs were evaluated during infection. Subclinical acute multifocal areas of hemorrhage and edema were noted in the lungs during infection; inactivation of regulatory T cells reduced the amount of pathologic foci. Expression of TNF was suppressed during the persistent phase of infection; inactivation of regulatory T cells eliminated the suppression of TNF. Taken together, these data suggest that regulatory T cells mediate Seoul virus persistence, possibly through elevated transcription and synthesis of TGF-beta and suppression of TNF. These data provide evidence of regulatory T cell involvement in the persistence of a zoonotic pathogen in its natural reservoir host.
| S-EPMC2000529 | biostudies-literature
Project description:Zoonotic influenza A viruses constantly pose a health threat to humans as novel strains occasionally emerge from the avian population to cause human infections. Many past epidemic as well as pandemic strains have originated from avian species. While most viruses are restricted to their primary hosts, zoonotic strains can sometimes arise from mutations or reassortment, leading them to acquire the capability to escape host species barrier and successfully infect a new host. Phylogenetic analyses and genetic markers are useful in tracing the origins of zoonotic infections, but there are still no effective means to identify high risk strains prior to an outbreak. Here we show that distinct host tropism protein signatures can be used to identify possible zoonotic strains in avian species which have the potential to cause human infections. We have discovered that influenza A viruses can now be classified into avian, human, or zoonotic strains based on their host tropism protein signatures. Analysis of all influenza A viruses with complete proteome using the host tropism prediction system, based on machine learning classifications of avian and human viral proteins has uncovered distinct signatures of zoonotic strains as mosaics of avian and human viral proteins. This is in contrast with typical avian or human strains where they show mostly avian or human viral proteins in their signatures respectively. Moreover, we have found that zoonotic strains from the same influenza outbreaks carry similar host tropism protein signatures characteristic of a common ancestry. Our results demonstrate that the distinct host tropism protein signature in zoonotic strains may prove useful in influenza surveillance to rapidly identify potential high risk strains circulating in avian species, which may grant us the foresight in anticipating an impending influenza outbreak.
| S-EPMC4767729 | biostudies-literature
Project description:Urban environments represent unique ecosystems where dense human populations may come into contact with wildlife species, some of which are established or potential reservoirs for zoonotic pathogens that cause human diseases. Finding practical ways to monitor the presence and/or abundance of zoonotic pathogens is important to estimate the risk of spillover to humans in cities. As brown rats (Rattus norvegicus) are ubiquitous in urban habitats, and are hosts of several zoonotic viruses, we conducted longitudinal sampling of brown rats in Vienna, Austria, a large population center in Central Europe. We investigated rat tissues for the presence of several zoonotic viruses, including flaviviruses, hantaviruses, coronaviruses, poxviruses, hepatitis E virus, encephalomyocarditis virus, and influenza A virus. Although we found no evidence of active infections (all were negative for viral nucleic acids) among 96 rats captured between 2016 and 2018, our study supports the findings of others, suggesting that monitoring urban rats may be an efficient way to estimate the activity of zoonotic viruses in urban environments.
| S-EPMC9316102 | biostudies-literature
Project description:A hallmark of disease is that most pathogens are able to infect more than one host species. However, for most pathogens, we still have a limited understanding of how this affects epidemiology, persistence and virulence of infections—including several zoonotic pathogens that reside in wild animal reservoirs and spillover into humans. In this chapter, we review the current knowledge of mallard (Anas platyrhynchos) as host for pathogens. This species is widely distributed, often occupying habitats close to humans and livestock, and is an important game bird species and the ancestor to domestic ducks—thereby being an excellent model species to highlight aspects of the wildlife, domestic animal interface and the relevance for human health. We discuss mallard as host for a range of pathogens but focus more in depth of it as a reservoir host for influenza A virus (IAV). Over the last decades, IAV research has surged, prompted in part to the genesis and spread of highly pathogenic virus variants that have been devastating to domestic poultry and caused a number of human spillover infections. The aim of this chapter is to synthesise and review the intricate interactions of virus, host and environmental factors governing IAV epidemiology and evolution.
| S-EPMC7123570 | biostudies-literature
Project description:Orthohantaviruses give rise to the emerging infections such as of hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in Eurasia and the Americas, respectively. In this review we will provide a comprehensive analysis of orthohantaviruses distribution and circulation in Eurasia and address the genetic diversity and evolution of Puumala orthohantavirus (PUUV), which causes HFRS in this region. Current data indicate that the geographical location and migration of the natural hosts can lead to the orthohantaviruses genetic diversity as the rodents adapt to the new environmental conditions. The data shows that a high level of diversity characterizes the genome of orthohantaviruses, and the PUUV genome is the most divergent. The reasons for the high genome diversity are mainly caused by point mutations and reassortment, which occur in the genome segments. However, it still remains unclear whether this diversity is linked to the disease's severity. We anticipate that the information provided in this review will be useful for optimizing and developing preventive strategies of HFRS, an emerging zoonosis with potentially very high mortality rates.
| S-EPMC7558059 | biostudies-literature