hAdV Dotaz Zobrazit nápovědu
Human adenoviruses (HAdV; species HAdV-A to -G) are highly prevalent in the human population, and represent an important cause of morbidity and, to a lesser extent, mortality. Recent studies have identified close relatives of these viruses in African great apes, suggesting that some HAdV may be of zoonotic origin. We analyzed more than 800 fecal samples from wild African great apes and humans to further investigate the evolutionary history and zoonotic potential of hominine HAdV. HAdV-B and -E were frequently detected in wild gorillas (55%) and chimpanzees (25%), respectively. Bayesian ancestral host reconstruction under discrete diffusion models supported a gorilla and chimpanzee origin for these viral species. Host switches were relatively rare along HAdV evolution, with about ten events recorded in 4.5 My. Despite presumably rare direct contact between sympatric populations of the two species, transmission events from gorillas to chimpanzees were observed, suggesting that habitat and dietary overlap may lead to fecal-oral cross-hominine transmission of HAdV. Finally, we determined that two independent HAdV-B transmission events to humans occurred more than 100,000 years ago. We conclude that HAdV-B circulating in humans are of zoonotic origin and have probably affected global human health for most of our species lifetime.
- MeSH
- Adenoviridae * genetika patogenita MeSH
- adenovirové infekce * genetika přenos MeSH
- druhová specificita MeSH
- Hominidae virologie MeSH
- lidé MeSH
- molekulární evoluce * MeSH
- zoonózy genetika přenos MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A surge in hematopoietic stem cell transplantation (HSCT) human adenovirus A31 (HAdV-A31) infections was initially observed in late 2014/2015 at SickKids (SK) Hospital, Toronto, Canada. In response, enhanced laboratory monitoring for all adenovirus infections was conducted. Positive samples underwent genotyping, viral culture, and, in selected cases, whole-genome sequencing (WGS). HAdV-A31 specimens/DNA obtained from four international pediatric HSCT centers also underwent WGS. During the SK outbreak period (27 October 2014 to 31 October 2018), 17/20 HAdV-A31 isolates formed a distinct clade with 0 to 8 mutations between the closest neighbors. Surveillance before and after the outbreak detected six additional HAdV-A31 HSCT cases; three of the four sequenced cases clustered within the outbreak clade. Two SK outbreak isolates were identical to sequences from two patients in an outbreak in England. Three SK non-outbreak sequences also had high sequence similarity to strains from three international centers. Environmental PCR testing of the HSCT ward showed significant adenovirus contamination. Despite intense infection control efforts, we observed re-occurrence of infection with the outbreak strain. Severe but nonfatal infection was observed more commonly with HAdV-A31 compared to other genotypes, except HAdV-C1. Our findings strongly implicate nosocomial spread of HAdV-A31 over 10 years on a HSCT unit and demonstrate the value of WGS in defining and mapping the outbreak. Close linkages among strains in different countries suggest international dissemination, though the mechanism is undetermined. This large, extended outbreak emphasizes the pre-eminent role of HAdV-A31 in causing intractable pediatric HSCT outbreaks of severe illness worldwide.
- MeSH
- adenovirové infekce lidí * epidemiologie MeSH
- adenovirové infekce * MeSH
- dítě MeSH
- fylogeneze MeSH
- lidé MeSH
- lidské adenoviry * MeSH
- nemocnice MeSH
- sekvenování celého genomu MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
V sezóně 2013/14 byly dominujícím respiračním patogenem adenoviry (hAdV). Adenoviry jsou poměrně bohatá skupina virů obsahujících dle současné klasifikace 60 sérotypů. Většina z nich je spojována s mnoha různými mírnými onemocněními od respiračních, přes gastroenteritidy až po encefalitidy. Pouze některé sérotypy vyvolávají závažné infekce s tendencí k lokálním epidemiím. Pro majoritní výskyt jsme přistoupili k charakterizaci hAdV v sentinelových materiálech. Namísto klasické sérotypizace byla použita metoda parciálního sekvenování úseku hexonového genu o velikosti cca 800 párů bazí. Na základě BLAST (Basic Local Alignment Search Tool) analýzy bylo provedeno systematické zařazení u celkem 27 materiálů z celkového počtu 52 vzorků. V rámci klasifikace bylo nalezeno pouze 5 sérotypů (3B, 2C, 1C, 7B, 4E). Naprosto převažujícím sérotypem byl hAdV 3B, který byl prokázán v 63 % sekvenovaných materiálů. V souvislosti s adenovirovým onemocněním udávali téměř všichni nemocní rýmu, horečku s teplotou nad 38 °C a kašel. Zhruba polovina nemocných trpělo bolestí hlavy a malátností. Nebyly prokázány žádné sérotypy dávané do souvislosti se závažným onemocněním, což odpovídá vybrané kohortě pacientů. Nejméně u poloviny materiálů byl sérotyp určen přímo z klinického materiálu bez předchozí izolace. Lze tedy shrnout, že sérotypizace /genotypizace provedená na základě parciálního sekvenování hexonového genu s použitím „nested“ (vnořených) primerů nevyžaduje izolaci viru na tkáňové kultuře. Metoda je dostupná a efektivní při charakterizaci adenovirů.
In the season 2013/14, the predominant respiratory pathogen was adenovirus (hAdV). Adenoviruses are a relatively large family of DNA viruses consisting of 60 serotypes classified into seven groups. Most of them are associated with many various mild diseases from respiratory infections through gastroenteritis to encephalitis. Some serotypes only cause severe infection with a tendency towards local outbreaks. We have implemented the classification of hAdV in sentinel samples. Instead of conventional serotyping, partial sequencing of the approximately 800 pb segments of the hexon gene was used. Based on the BLAST (Basic Local Alignment Search Tool) analysis, 27 of 52 samples were fitted into the current classification system. Only five serotypes were found (3B, 2C, 1C, 7B, 4E). The clearly prevailing hAdV serotype was 3B, detected in 63 % of the samples sequenced. Nearly all patients with adenovirus infection reported runny nose, temperature above 38°C, and cough. About half of the patients complained of headache and malaise. No severe disease-associated serotype was detected, as expected given the selected cohort of patients. In at least half of the samples, the serotype was determined without the need for virus isolation on cell culture. It can be concluded that serotyping based on partial hexon gene sequencing in combination with nested PCR does not require virus isolation on tissue culture. The method is time saving and effective in the characterization of adenoviruses.
- Klíčová slova
- genotypizace,
- MeSH
- Adenoviridae genetika MeSH
- adenovirové infekce lidí * diagnóza genetika MeSH
- DNA primery MeSH
- genotypizační techniky MeSH
- infekce dýchací soustavy * diagnóza etiologie MeSH
- lidé MeSH
- sekvenční analýza DNA MeSH
- sérotypizace * metody statistika a číselné údaje MeSH
- Check Tag
- lidé MeSH
Oncolytic virotherapies (OV) hold immense clinical potential. OV based on human adenoviruses (HAdV) derived from HAdV with naturally low rates of pre-existing immunity will be beneficial for future clinical translation. We generated a low-seroprevalence HAdV-D10 serotype vector incorporating an αvβ6 integrin-selective peptide, A20, to target αvβ6-positive tumor cell types. HAdV-D10 has limited natural tropism. Structural and biological studies of HAdV-D10 knob protein highlighted low-affinity engagement with native adenoviral receptors CAR and sialic acid. HAdV-D10 fails to engage blood coagulation factor X, potentially eliminating "off-target" hepatic sequestration in vivo. We engineered an A20 peptide that selectively binds αvβ6 integrin into the DG loop of HAdV-D10 fiber knob. Assays in αvβ6+ cancer cell lines demonstrated significantly increased transduction mediated by αvβ6-targeted variants compared with controls, confirmed microscopically. HAdV-D10.A20 resisted neutralization by neutralizing HAdV-C5 sera. Systemic delivery of HAdV-D10.A20 resulted in significantly increased GFP expression in BT20 tumors. Replication-competent HAdV-D10.A20 demonstrated αvβ6 integrin-selective cell killing in vitro and in vivo. HAdV-D10 possesses characteristics of a promising virotherapy, combining low seroprevalence, weak receptor interactions, and reduced off-target uptake. Incorporation of an αvβ6 integrin-selective peptide resulted in HAdV-D10.A20, with significant potential for clinical translation.
- Publikační typ
- časopisecké články MeSH
UNLABELLED: Adenovirus (AdV) infection of the respiratory epithelium is common but poorly understood. Human AdV species C types, such as HAdV-C5, utilize the Coxsackie-adenovirus receptor (CAR) for attachment and subsequently integrins for entry. CAR and integrins are however located deep within the tight junctions in the mucosa where they would not be easily accessible. Recently, a model for CAR-independent AdV entry was proposed. In this model, human lactoferrin (hLF), an innate immune protein, aids the viral uptake into epithelial cells by mediating interactions between the major capsid protein, hexon, and yet unknown host cellular receptor(s). However, a detailed understanding of the molecular interactions driving this mechanism is lacking. Here, we present a new cryo-EM structure of HAdV-5C hexon at high resolution alongside a hybrid structure of HAdV-5C hexon complexed with human lactoferrin (hLF). These structures reveal the molecular determinants of the interaction between hLF and HAdV-C5 hexon. hLF engages hexon primarily via its N-terminal lactoferricin (Lfcin) region, interacting with hexon's hypervariable region 1 (HVR-1). Mutational analyses pinpoint critical Lfcin contacts and also identify additional regions within hLF that critically contribute to hexon binding. Our study sheds more light on the intricate mechanism by which HAdV-C5 utilizes soluble hLF/Lfcin for cellular entry. These findings hold promise for advancing gene therapy applications and inform vaccine development. IMPORTANCE: Our study delves into the structural aspects of adenovirus (AdV) infections, specifically HAdV-C5 in the respiratory epithelium. It uncovers the molecular details of a novel pathway where human lactoferrin (hLF) interacts with the major capsid protein, hexon, facilitating viral entry, and bypassing traditional receptors such as CAR and integrins. The study's cryo-EM structures reveal how hLF engages hexon, primarily through its N-terminal lactoferricin (Lfcin) region and hexon's hypervariable region 1 (HVR-1). Mutational analyses identify critical Lfcin contacts and other regions within hLF vital for hexon binding. This structural insight sheds light on HAdV-C5's mechanism of utilizing soluble hLF/Lfcin for cellular entry, holding promise for gene therapy and vaccine development advancements in adenovirus research.
- MeSH
- adenovirové infekce lidí metabolismus virologie MeSH
- biologické modely MeSH
- elektronová kryomikroskopie MeSH
- internalizace viru * MeSH
- laktoferrin * chemie genetika metabolismus ultrastruktura MeSH
- lidé MeSH
- lidské adenoviry * chemie genetika metabolismus ultrastruktura MeSH
- mutace MeSH
- respirační sliznice cytologie metabolismus virologie MeSH
- rozpustnost MeSH
- vazba proteinů MeSH
- vazebná místa genetika MeSH
- virové plášťové proteiny * chemie genetika metabolismus ultrastruktura MeSH
- virové receptory * chemie genetika metabolismus ultrastruktura MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
In recent years, numerous foodborne outbreaks due to consumption of berry fruit contaminated by human enteric viruses have been reported. This European multinational study investigated possible contamination routes by monitoring the entire food chain for a panel of human and animal enteric viruses. A total of 785 samples were collected throughout the food production chain of four European countries (Czech Republic, Finland, Poland and Serbia) during two growing seasons. Samples were taken during the production phase, the processing phase, and at point-of-sale. Samples included irrigation water, animal faeces, food handlers' hand swabs, swabs from toilets on farms, from conveyor belts at processing plants, and of raspberries or strawberries at points-of-sale; all were subjected to virus analysis. The samples were analysed by real-time (reverse transcription, RT)-PCR, primarily for human adenoviruses (hAdV) to demonstrate that a route of contamination existed from infected persons to the food supply chain. The analyses also included testing for the presence of selected human (norovirus, NoV GI, NoV GII and hepatitis A virus, HAV), animal (porcine adenovirus, pAdV and bovine polyomavirus, bPyV) and zoonotic (hepatitis E virus, HEV) viruses. At berry production, hAdV was found in 9.5%, 5.8% and 9.1% of samples of irrigation water, food handlers' hands and toilets, respectively. At the processing plants, hAdV was detected in one (2.0%) swab from a food handler's hand. At point-of-sale, the prevalence of hAdV in fresh raspberries, frozen raspberries and fresh strawberries, was 0.7%, 3.2% and 2.0%, respectively. Of the human pathogenic viruses, NoV GII was detected in two (3.6%) water samples at berry production, but no HAV was detected in any of the samples. HEV-contaminated frozen raspberries were found once (2.6%). Animal faecal contamination was evidenced by positive pAdV and bPyV assay results. At berry production, one water sample contained both viruses, and at point-of-sale 5.7% and 1.3% of fresh and frozen berries tested positive for pAdV. At berry production hAdV was found both in irrigation water and on food handler's hands, which indicated that these may be important vehicles by which human pathogenic viruses enter the berry fruit chain. Moreover, both zoonotic and animal enteric viruses could be detected on the end products. This study gives insight into viral sources and transmission routes and emphasizes the necessity for thorough compliance with good agricultural and hygienic practice at the farms to help protect the public from viral infections.
- MeSH
- adenoviry prasat izolace a purifikace MeSH
- Enterovirus MeSH
- epidemický výskyt choroby MeSH
- feces virologie MeSH
- kontaminace potravin analýza MeSH
- lidé MeSH
- lidské adenoviry izolace a purifikace MeSH
- manipulace s potravinami metody MeSH
- mikrobiologie vody MeSH
- Norovirus izolace a purifikace MeSH
- ovoce virologie MeSH
- Polyomavirus izolace a purifikace MeSH
- prasata MeSH
- ruka virologie MeSH
- skot MeSH
- virus hepatitidy A izolace a purifikace MeSH
- virus hepatitidy E izolace a purifikace MeSH
- viry MeSH
- zásobování potravinami MeSH
- zemědělské zavlažování MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Finsko MeSH
- Polsko MeSH
- Srbsko MeSH
BACKGROUND: The role of viral infections in preterm prelabor rupture of the membranes (PPROM) is not established. Studies on the presence of viral genomes in the amniotic fluid (AF) collected in pregnancies complicated by PPROM show contradictory outcomes. OBJECTIVES: To investigate AF samples of PPROM pregnancies for the presence of viral genomes. STUDY DESIGN: AF samples from patients with PPROM were collected during a 4-year (2008-2012) observational study. 174 women were included with selection criteria of singleton pregnancy, PPROM, and maternal age of 18 years and above. PCR was used for detection of human cytomegalovirus (HCMV), herpes simplex virus (HSV), parvovirus B19, human adenoviruses (HAdV), enteroviruses (EV) and human parechovirus (HPeV). The selection of these viral targets was based on literature regarding screening of AF for presence of viral genomes. RESULTS: Only a single sample was positive out of the 174 tested AFs, HCMV DNA was detected. CONCLUSIONS: PPROM is not associated with active viral infections.
Fresh produce that is contaminated with viruses may lead to infection and viral gastroenteritis or hepatitis when consumed raw. It is thus important to reduce virus numbers on these foods. Prevention of virus contamination in fresh produce production and processing may be more effective than treatment, as sufficient virus removal or inactivation by post-harvest treatment requires high doses that may adversely affect food quality. To date knowledge of the contribution of various potential contamination routes is lacking. A risk assessment model was developed for human norovirus, hepatitis A virus and human adenovirus in raspberry and salad vegetable supply chains to quantify contributions of potential contamination sources to the contamination of produce at retail. These models were used to estimate public health risks. Model parameterization was based on monitoring data from European supply chains and literature data. No human pathogenic viruses were found in the soft fruit supply chains; human adenovirus (hAdV) was detected, which was additionally monitored as an indicator of fecal pollution to assess the contribution of potential contamination points. Estimated risks per serving of lettuce based on the models were 3×10(-4) (6×10(-6)-5×10(-3)) for NoV infection and 3×10(-8) (7×10(-10)-3×10(-6)) for hepatitis A jaundice. The contribution to virus contamination of hand-contact was larger as compared with the contribution of irrigation, the conveyor belt or the water used for produce rinsing. In conclusion, viral contamination in the lettuce and soft fruit supply chains occurred and estimated health risks were generally low. Nevertheless, the 97.5% upper limit for the estimated NoV contamination of lettuce suggested that infection risks up to 50% per serving might occur. Our study suggests that attention to full compliance for hand hygiene will improve fresh produce safety related to virus risks most as compared to the other examined sources, given the monitoring results. This effect will be further aided by compliance with other hygiene and water quality regulations in production and processing facilities.
- MeSH
- hepatitida A prevence a kontrola MeSH
- hodnocení rizik MeSH
- hygiena rukou MeSH
- infekce viry z čeledi Caliciviridae prevence a kontrola MeSH
- kvalita vody MeSH
- lidé MeSH
- lidské adenoviry izolace a purifikace fyziologie MeSH
- Norovirus izolace a purifikace fyziologie MeSH
- ovoce virologie MeSH
- salát (hlávkový) virologie MeSH
- teoretické modely * MeSH
- virus hepatitidy A izolace a purifikace fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
