The source, timing, and geographical origin of the 1918–1920 pandemic influenza A virus have remained tenaciously obscure for nearly a century, as have the reasons for its unusual severity among ...young adults. Here, we reconstruct the origins of the pandemic virus and the classic swine influenza and (postpandemic) seasonal H1N1 lineages using a host-specific molecular clock approach that is demonstrably more accurate than previous methods. Our results suggest that the 1918 pandemic virus originated shortly before 1918 when a human H1 virus, which we infer emerged before ∼1907, acquired avian N1 neuraminidase and internal protein genes. We find that the resulting pandemic virus jumped directly to swine but was likely displaced in humans by ∼1922 by a reassortant with an antigenically distinct H1 HA. Hence, although the swine lineage was a direct descendent of the pandemic virus, the post-1918 seasonal H1N1 lineage evidently was not, at least for HA. These findings help resolve several seemingly disparate observations from 20th century influenza epidemiology, seroarcheology, and immunology. The phylogenetic results, combined with these other lines of evidence, suggest that the high mortality in 1918 among adults aged ∼20 to ∼40 y may have been due primarily to their childhood exposure to a doubly heterosubtypic putative H3N8 virus, which we estimate circulated from ∼1889–1900. All other age groups (except immunologically naive infants) were likely partially protected by childhood exposure to N1 and/or H1-related antigens. Similar processes may underlie age-specific mortality differences between seasonal H1N1 vs. H3N2 and human H5N1 vs. H7N9 infections.
Worldwide, ticks are important vectors of human and animal pathogens. Besides Lyme Borreliosis, a variety of other bacterial and protozoal tick-borne infections are of medical interest in Europe. In ...this study, 553 questing and feeding Ixodes ricinus (n = 327) and Dermacentor reticulatus ticks (n = 226) were analysed by PCR for Borrelia, Rickettsia, Anaplasma, Coxiella, Francisella and Babesia species. Overall, the pathogen prevalence in ticks was 30.6% for I. ricinus and 45.6% for D. reticulatus. The majority of infections were caused by members of the spotted-fever group rickettsiae (24.4%), 9.4% of ticks were positive for Borrelia burgdorferi sensu lato, with Borrelia afzelii being the most frequently detected species (40.4%). Pathogens with low prevalence rates in ticks were Anaplasma phagocytophilum (2.2%), Coxiella burnetii (0.9%), Francisella tularensis subspecies (0.7%), Bartonella henselae (0.7%), Babesia microti (0.5%) and Babesia venatorum (0.4%). On a regional level, hotspots of pathogens were identified for A. phagocytophilum (12.5-17.2%), F. tularensis ssp. (5.5%) and C. burnetii (9.1%), suggesting established zoonotic cycles of these pathogens at least at these sites. Our survey revealed a high burden of tick-borne pathogens in questing and feeding I. ricinus and D. reticulatus ticks collected in different regions in Belarus, indicating a potential risk for humans and animals. Identified hotspots of infected ticks should be included in future surveillance studies, especially when F. tularensis ssp. and C. burnetii are involved.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Since 2005, the Pathogen–Host Interactions Database (PHI-base) has manually curated experimentally verified pathogenicity, virulence and effector genes from fungal, bacterial and protist ...pathogens, which infect animal, plant, fish, insect and/or fungal hosts. PHI-base (www.phi-base.org) is devoted to the identification and presentation of phenotype information on pathogenicity and effector genes and their host interactions. Specific gene alterations that did not alter the in host interaction phenotype are also presented. PHI-base is invaluable for comparative analyses and for the discovery of candidate targets in medically and agronomically important species for intervention. Version 4.12 (September 2021) contains 4387 references, and provides information on 8411 genes from 279 pathogens, tested on 228 hosts in 18, 190 interactions. This provides a 24% increase in gene content since Version 4.8 (September 2019). Bacterial and fungal pathogens represent the majority of the interaction data, with a 54:46 split of entries, whilst protists, protozoa, nematodes and insects represent 3.6% of entries. Host species consist of approximately 54% plants and 46% others of medical, veterinary and/or environmental importance. PHI-base data is disseminated to UniProtKB, FungiDB and Ensembl Genomes. PHI-base will migrate to a new gene-centric version (version 5.0) in early 2022. This major development is briefly described.
CD4
effector lymphocytes (T
) are traditionally classified by the cytokines they produce. To determine the states that T
cells actually adopt in frontline tissues in vivo, we applied single-cell ...transcriptome and chromatin analyses to colonic T
cells in germ-free or conventional mice or in mice after challenge with a range of phenotypically biasing microbes. Unexpected subsets were marked by the expression of the interferon (IFN) signature or myeloid-specific transcripts, but transcriptome or chromatin structure could not resolve discrete clusters fitting classic helper T cell (T
) subsets. At baseline or at different times of infection, transcripts encoding cytokines or proteins commonly used as T
markers were distributed in a polarized continuum, which was functionally validated. Clones derived from single progenitors gave rise to both IFN-γ- and interleukin (IL)-17-producing cells. Most of the transcriptional variance was tied to the infecting agent, independent of the cytokines produced, and chromatin variance primarily reflected activities of activator protein (AP)-1 and IFN-regulatory factor (IRF) transcription factor (TF) families, not the canonical subset master regulators T-bet, GATA3 or RORγ.
Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the ...beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs.
Congenital infections with pathogens such as Zika virus, Toxoplasma gondii, Listeria monocytogenes, Treponema pallidium, parvovirus, HIV, varicella zoster virus, Rubella, Cytomegalovirus, and ...Herpesviruses are a major cause of morbidity and mortality worldwide. Despite the devastating impact of microbial infections on the developing fetus, relatively little is known about how pathogens associated with congenital disease breach the placental barrier to transit vertically during human pregnancy. In this Review, we focus on transplacental transmission of pathogens during human gestation. We introduce the structure of the human placenta and describe the innate mechanisms by which the placenta restricts microbial access to the intrauterine compartment. Based on current knowledge, we also discuss the potential pathways employed by microorganisms to overcome the placental barrier and prospects for the future.
In this Review, Arora et al. focus on proposed antenatal mechanisms of transplacental transmission of known “TORCH” pathogens including Toxoplasma gondii, Listeria monocytogenes, Rubella, Cytomegalovirus, and Herpesviruses, and more recently Zika virus. They also discuss the innate mechanisms by which the placenta restricts microbial access to the intrauterine compartment
Neurotropic viruses can cause devastating central nervous system (CNS) infections, especially in young children and the elderly. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid ...barrier (BCSFB) have been described as relevant sites of entry for specific viruses as well as for leukocytes, which are recruited during the proinflammatory response in the course of CNS infection. In this review, we illustrate examples of established brain barrier models, in which the specific reaction patterns of different viral families can be analyzed. Furthermore, we highlight the pathogen specific array of cytokines and chemokines involved in immunological responses in viral CNS infections. We discuss in detail the link between specific cytokines and chemokines and leukocyte migration profiles. The thorough understanding of the complex and interrelated inflammatory mechanisms as well as identifying universal mediators promoting CNS inflammation is essential for the development of new diagnostic and treatment strategies.
Three common systemic human fungal pathogens —Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus — have retained all the machinery to engage in sexual reproduction, and yet their ...populations are often clonal with limited evidence for recombination. Striking parallels have emerged with four protozoan parasites that infect humans: Toxoplasma gondii, Trypanosoma brucei, Trypanosoma cruzi and Plasmodium falciparum. Limiting sexual reproduction appears to be a common virulence strategy, enabling generation of clonal populations well adapted to host and environmental niches, yet retaining the ability to engage in sexual or parasexual reproduction and respond to selective pressure. Continued investigation of the sexual nature of microbial pathogens should facilitate both laboratory investigation and an understanding of the complex interplay between pathogens, hosts, vectors, and their environments.
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