Disease Transmission To Humans Research Articles

Biofilms and human health.

A biofilm can be defined as a surface-attached (sessile) community of microorganisms embedded and growing in a self-produced matrix of extracellular polymeric substances. These biofilm communities can be found in medical, industrial and natural environments, and can also be engineered in vitro for various biotechnological applications. Biofilms play a significant role in the transmission and persistence of human disease especially for diseases associated with inert surfaces, including medical devices for internal or external use. Biofilm infections on implants or in-dwelling devices are difficult to eradicate because of their much better protection against macrophages and antibiotics, compared to free living cells, leading to severe clinical complications often with lethal outcome. Recent developments in nanotechnology have provided novel approaches to preventing and dispersing biofilm related infections and potentially providing a novel method for fighting infections that is nondrug related.

On palms, bugs, and Chagas disease in the Americas

Palms are ubiquitous across Neotropical landscapes, from pristine forests or savannahs to large cities. Although palms provide useful ecosystem services, they also offer suitable habitat for triatomines and for Trypanosoma cruzi mammalian hosts. Wild triatomines often invade houses by flying from nearby palms, potentially leading to new cases of human Chagas disease. Understanding and predicting triatomine-palm associations and palm infestation probabilities is important for enhancing Chagas disease prevention in areas where palm-associated vectors transmit T. cruzi. We present a comprehensive overview of palm infestation by triatomines in the Americas, combining a thorough reanalysis of our published and unpublished records with an in-depth review of the literature. We use site-occupancy modeling (SOM) to examine infestation in 3590 palms sampled with non-destructive methods, and standard statistics to describe and compare infestation in 2940 palms sampled by felling-and-dissection. Thirty-eight palm species (18 genera) have been reported to be infested by ∼39 triatomine species (10 genera) from the USA to Argentina. Overall infestation varied from 49.1–55.3% (SOM) to 62.6–66.1% (dissection), with important heterogeneities among sub-regions and particularly among palm species. Large palms with complex crowns (e.g., Attalea butyracea, Acrocomia aculeata) and some medium-crowned palms (e.g., Copernicia, Butia) are often infested; in slender, small-crowned palms (e.g., Euterpe) triatomines associate with vertebrate nests. Palm infestation tends to be higher in rural settings, but urban palms can also be infested. Most Rhodnius species are probably true palm specialists, whereas Psammolestes, Eratyrus, Cavernicola, Panstrongylus, Triatoma, Alberprosenia, and some Bolboderini seem to use palms opportunistically. Palms provide extensive habitat for enzootic T. cruzi cycles and a critical link between wild cycles and transmission to humans. Unless effective means to reduce contact between people and palm-living triatomines are devised, palms will contribute to maintaining long-term and widespread, albeit possibly low-intensity, transmission of human Chagas disease.

Description of Lutzomyia (Trichophoromyia) nautaensis n. sp. (Diptera: Psychodidae) from the Peruvian Amazon Basin.

A new species of sand fly, which we describe as Lutzomyia (Trichophoromyia) nautaensis n. sp., was collected in the northern Peruvian Amazon Basin. In this region of Peru, cutaneous leishmaniasis is transmitted primarily by anthropophilic sand flies; however, zoophilic sand flies of the subgenus Trichophoromyia may also be incriminated in disease transmission. Detection of Leishmania spp. in Lutzomyia auraensis Mangabeira captured in the southern Peruvian Amazon indicates the potential of this and other zoophilic sand flies for human disease transmission, particularly in areas undergoing urban development. Herein, we describe Lutzomyia (Trichophoromyia) nautaensis n. sp., and report new records of sand flies in Peru.

Spread of Leishmania infantum in Europe with dog travelling

Leishmania infantum is the etiological agent of canine leishmaniosis (CanL) in Europe, where it is endemic in the Mediterranean region, with dogs being considered the major reservoir of the parasite for humans and other mammalian hosts. The main transmission mode of Leishmania is by the bite of infected phlebotomine sand fly insects (genus Phlebotomus), which are the only proven vectors of this zoonotic protozoan. Less common, non-vectorial transmission between dogs include infection through transfused blood products from infected donors, transplacental and venereal transmission. CanL has exhibited an expansion to new locations in Europe, mainly northwards, either by territorial contiguity, often in association with global warming that favours vectorial transmission, or by the long-distance importation of infected dogs. The increasing incidence of CanL in countries where the disease is not endemic is challenging owners, veterinarians and government authorities. Most infected dogs in these new areas have been relocated from or travelled with their owners to endemic regions, but in some cases transmission might have also been autochthonous. In the absence of prophylactic measures, the introduction of infected dogs in areas previously free of endemic CanL but which have competent sand fly vectors can result in a potential persistence of L. infantum. The spread of L. infantum in Europe is reviewed with a focus on transmission, epidemiology and geographic distribution of endemic and non-endemic CanL, infection and disease in humans and animal hosts other than dogs, together with prevention and additional control strategies.

Forensic analysis of the microbiome of phones and shoes

BackgroundMicrobial interaction between human-associated objects and the environments we inhabit may have forensic implications, and the extent to which microbes are shared between individuals inhabiting the same space may be relevant to human health and disease transmission. In this study, two participants sampled the front and back of their cell phones, four different locations on the soles of their shoes, and the floor beneath them every waking hour over a 2-day period. A further 89 participants took individual samples of their shoes and phones at three different scientific conferences.ResultsSamples taken from different surface types maintained significantly different microbial community structures. The impact of the floor microbial community on that of the shoe environments was strong and immediate, as evidenced by Procrustes analysis of shoe replicates and significant correlation between shoe and floor samples taken at the same time point. Supervised learning was highly effective at determining which participant had taken a given shoe or phone sample, and a Bayesian method was able to determine which participant had taken each shoe sample based entirely on its similarity to the floor samples. Both shoe and phone samples taken by conference participants clustered into distinct groups based on location, though much more so when an unweighted distance metric was used, suggesting sharing of low-abundance microbial taxa between individuals inhabiting the same space.ConclusionsCorrelations between microbial community sources and sinks allow for inference of the interactions between humans and their environment.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-015-0082-9) contains supplementary material, which is available to authorized users.

Selective Elimination of Mitochondrial Mutations in the Germline by Genome Editing

Mitochondrial diseases include a group of maternally inherited genetic disorders caused by mutations in mtDNA. In most of these patients, mutated mtDNA coexists with wild-type mtDNA, a situation known as mtDNA heteroplasmy. Here, we report on a strategy toward preventing germline transmission of mitochondrial diseases by inducing mtDNA heteroplasmy shift through the selective elimination of mutated mtDNA. As a proof of concept, we took advantage of NZB/BALB heteroplasmic mice, which contain two mtDNA haplotypes, BALB and NZB, and selectively prevented their germline transmission using either mitochondria-targeted restriction endonucleases or TALENs. In addition, we successfully reduced human mutated mtDNA levels responsible for Leber's hereditary optic neuropathy (LHOND), and neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP), in mammalian oocytes using mitochondria-targeted TALEN (mito-TALENs). Our approaches represent a potential therapeutic avenue for preventing the transgenerational transmission of human mitochondrial diseases caused by mutations in mtDNA. PAPERCLIP.

Serologic screening for 13 infectious agents in roe deer (Capreolus capreolus) in Flanders

IntroductionIn order to investigate the role of roe deer in the maintenance and transmission of infectious animal and human diseases in Flanders, we conducted a serologic screening in 12 hunting areas.Materials and methodsRoe deer sera collected between 2008 and 2013 (n=190) were examined for antibodies against 13 infectious agents, using indirect enzyme-linked immunosorbent assay, virus neutralisation, immunofluorescence, or microagglutination test, depending on the agent.Results and discussionHigh numbers of seropositives were found for Anaplasma phagocytophilum (45.8%), Toxoplasma gondii (43.2%) and Schmallenberg virus (27.9%), the latter with a distinct temporal distribution pattern following the outbreak in domestic ruminants. Lower antibody prevalence was found for Chlamydia abortus (6.7%), tick-borne encephalitis virus (5.1%), Neospora caninum (4.8%), and Mycobacterium avium subsp paratuberculosis (4.1%). The lowest prevalences were found for Leptospira (1.7%), bovine viral diarrhoea virus 1 (1.3%), and Coxiella burnetii (1.2%). No antibodies were found against Brucella sp., bovine herpesvirus 1, and bluetongue virus. A significant difference in seroprevalence between ages (higher in adults >1 year) was found for N. caninum. Four doubtful reacting sera accounted for a significant difference in seroprevalence between sexes for C. abortus (higher in females).ConclusionsDespite the more intensive landscape use in Flanders, the results are consistent with other European studies. Apart from maintaining C. abortus and MAP, roe deer do not seem to play an important role in the epidemiology of the examined zoonotic and domestic animal pathogens. Nevertheless, their meaning as sentinels should not be neglected in the absence of other wild cervid species.

Capacity of mosquitoes to transmit malaria depends on larval environment.

BackgroundAdult traits of holometabolous insects such as reproduction and survival can be shaped by conditions experienced during larval development. These “carry-over” effects influence not only individual life history and fitness, but can also impact interactions between insect hosts and parasites. Despite this, the implications of larval conditions for the transmission of human, wildlife and plant diseases that are vectored by insects remain poorly understood.MethodsWe used Anopheles stephensi mosquitoes and the rodent malaria, Plasmodium yoelii yoelii, to investigate whether quality of larval habitat influenced vectorial capacity of adult mosquitoes. Larvae were reared under two dietary conditions; one group received a diet commonly used for colony maintenance (0.3 mg/individual/day of Tetrafin fish food) while the other group received a reduced food diet (0.1 mg/individual/day). Upon emergence, adults were provided an infectious blood feed. We assessed the effects of diet on a range of larval and adult traits including larval development times and survival, number of emerging adults, adult body size and survival, gonotrophic cycle length, and mating success. We also estimated the effects of larval diet on parasite infection rates and growth kinetics within the adult mosquitoes.ResultsLarval dietary regime affected larval survival and development, as well as size, reproductive success and survival of adult mosquitoes. Larval diet also affected the intensity of initial Plasmodium infection (oocyst stage) and parasite replication, but without differences in overall infection prevalence at either the oocyst or sporozoite stage.ConclusionsTogether, the combined effects led to a relative reduction in vectorial capacity (a measure of the transmission potential of a mosquito population) in the low food treatment of 70%. This study highlights the need to consider environmental variation at the larval stages to better understand transmission dynamics and control of vector-borne diseases.

Human and bovine viruses in the Milwaukee River watershed: Hydrologically relevant representation and relations with environmental variables

To examine the occurrence, hydrologic variability, and seasonal variability of human and bovine viruses in surface water, three stream locations were monitored in the Milwaukee River watershed in Wisconsin, USA, from February 2007 through June 2008. Monitoring sites included an urban subwatershed, a rural subwatershed, and the Milwaukee River at the mouth. To collect samples that characterize variability throughout changing hydrologic periods, a process control system was developed for unattended, large-volume (56–2800L) filtration over extended durations. This system provided flow-weighted mean concentrations during runoff and extended (24-h) low-flow periods. Human viruses and bovine viruses were detected by real-time qPCR in 49% and 41% of samples (n=63), respectively. All human viruses analyzed were detected at least once including adenovirus (40% of samples), GI norovirus (10%), enterovirus (8%), rotavirus (6%), GII norovirus (1.6%) and hepatitis A virus (1.6%). Three of seven bovine viruses analyzed were detected including bovine polyomavirus (32%), bovine rotavirus (19%), and bovine viral diarrhea virus type 1 (5%). Human viruses were present in 63% of runoff samples resulting from precipitation and snowmelt, and 20% of low-flow samples. Maximum human virus concentrations exceeded 300genomiccopies/L. Bovine viruses were present in 46% of runoff samples resulting from precipitation and snowmelt and 14% of low-flow samples. The maximum bovine virus concentration was 11genomiccopies/L. Statistical modeling indicated that stream flow, precipitation, and season explained the variability of human viruses in the watershed, and hydrologic condition (runoff event or low-flow) and season explained the variability of the sum of human and bovine viruses; however, no model was identified that could explain the variability of bovine viruses alone. Understanding the factors that affect virus fate and transport in rivers will aid watershed management for minimizing human exposure and disease transmission.

Anthropogenic land use change and infectious diseases: a review of the evidence.

Humans have altered ecosystems worldwide, and it is important to understand how this land use change impacts infectious disease transmission in humans and animals. We conducted a systematic review 305 scientific articles investigating how specific types of anthropogenic land use change influence infectious disease dynamics. We summarized findings, highlighted common themes, and drew attention to neglected areas of research. There was an increase in publications on this topic over the last 30 years spanning diseases of humans, livestock, and wildlife, including a large number of zoonotic pathogens. Most papers (66.9%) were observational, 30.8% were review or concept papers, and few studies (2.3%) were experimental in nature, with most studies focusing on vector-borne and/or multi-host pathogens. Common land use change types related to disease transmission were deforestation/forest fragmentation/habitat fragmentation, agricultural development/irrigation, and urbanization/suburbanization. In response to anthropogenic change, more than half of the studies (56.9%) documented increased pathogen transmission, 10.4% of studies observed decreased pathogen transmission, 30.4% had variable and complex pathogen responses, and 2.4% showed no detectable changes. Commonly reported mechanisms by which land use change altered infectious disease transmission included alteration of the vector, host, and pathogen niche, changes in host and vector community composition, changes in behavior or movement of vectors and/or hosts, altered spatial distribution of hosts and/or vectors, and socioeconomic factors, and environmental contamination. We discussed observed patterns in the literature and make suggestions for future research directions, emphasizing the importance of ecological and evolutionary theory to understand pathogen responses in changing landscapes.

Human prion diseases and the risk of their transmission during anatomical dissection.

Prion diseases (or transmissible spongiform encephalopathies) are a unique group of fatal progressive neurodegenerative diseases of the central nervous system. The infectious agent is hypothesized to consist solely of a highly protease-resistant misfolded isoform of the host prion protein. Prions display a remarkable degree of resistance to chemical and physical decontamination. Many common forms of decontamination or neutralization used in infection control are ineffective against prions, except chaotropic agents that specifically disrupt proteins. Human cadaveric prosection or dissection for the purposes of teaching and demonstration of human anatomy has a distinguished history and remains one of the fundamentals of medical education. Iatrogenic transmission of human prion diseases has been demonstrated from the inoculation or implantation of human tissues. Therefore, although the incidence of human prion diseases is rare, restrictions exist upon the use of tissues from patients reported with dementia, specifically the brain and other central nervous system material. A current concern is the potential for asymptomatic variant Creutzfeldt-Jakob disease transmission within the UK population. Therefore, despite the preventative measures, the transmission of prion disease through human tissues remains a potential risk to those working with these materials. In this review, we aim to summarize the current knowledge on human prion disease relevant to those working with human tissues in the context of anatomical dissection.

Domesticated animals and human infectious diseases of zoonotic origins: Domestication time matters

The rate of emergence for emerging infectious diseases has increased dramatically over the last century, and research findings have implicated wildlife as an importance source of novel pathogens. However, the role played by domestic animals as amplifiers of pathogens emerging from the wild could also be significant, influencing the human infectious disease transmission cycle. The impact of domestic hosts on human disease emergence should therefore be ascertained. Here, using three independent datasets we showed positive relationships between the time since domestication of the major domesticated mammals and the total number of parasites or infectious diseases they shared with humans. We used network analysis, to better visualize the overall interactions between humans and domestic animals (and amongst animals) and estimate which hosts are potential sources of parasites/pathogens for humans (and for all other hosts) by investigating the network architecture. We used centrality, a measure of the connection amongst each host species (humans and domestic animals) in the network, through the sharing of parasites/pathogens, where a central host (i.e. high value of centrality) is the one that is infected by many parasites/pathogens that infect many other hosts in the network. We showed that domesticated hosts that were associated a long time ago with humans are also the central ones in the network and those that favor parasites/pathogens transmission not only to humans but also to all other domesticated animals. These results urge further investigation of the diversity and origin of the infectious diseases of domesticated animals in their domestication centres and the dispersal routes associated with human activities. Such work may help us to better understand how domesticated animals have bridged the epidemiological gap between humans and wildlife.

Healthy Animals, Healthy People: Zoonosis Risk from Animal Contact in Pet Shops, a Systematic Review of the Literature

BackgroundAround 67 million pets are owned by households in the United Kingdom, and an increasing number of these are exotic animals. Approximately a third of pets are purchased through retail outlets or direct from breeders. A wide range of infections can be associated with companion animals.ObjectivesThis study uses a systematic literature review to describe the transmission of zoonotic disease in humans associated with a pet shop or other location selling pets (incidents of rabies tracebacks and zoonoses from pet food were excluded).Data sourcesPubMed and EMBASE.ResultsFifty seven separate case reports or incidents were described in the 82 papers that were identified by the systematic review. Summary information on each incident is included in this manuscript. The infections include bacterial, viral and fungal diseases and range in severity from mild to life threatening. Infections associated with birds and rodents were the most commonly reported. Over half of the reports describe incidents in the Americas, and three of these were outbreaks involving more than 50 cases. Many of the incidents identified relate to infections in pet shop employees.LimitationsThis review may have been subject to publication bias, where unusual and unexpected zoonotic infections may be over-represented in peer-reviewed publications. It was also restricted to English-language articles so that pathogens that are more common in non-Western countries, or in more exotic animals not common in Europe and the Americas, may have been under-represented.Conclusions/implicationsA wide spectrum of zoonotic infections are acquired from pet shops. Salmonellosis and psittacosis were the most commonly documented diseases, however more unusual infections such as tularemia also appeared in the review. Given their potential to spread zoonotic infection, it is important that pet shops act to minimise the risk as far as possible.

Reduced survival and reproductive success generates selection pressure for the dengue mosquito Aedes aegypti to evolve resistance against infection by the microsporidian parasite Vavraia culicis

The success and sustainability of control measures aimed at reducing the transmission of mosquito-borne diseases will depend on how they influence the fitness of mosquitoes in targeted populations. We investigated the effects of the microsporidian parasite Vavraia culicis on the survival, blood-feeding behaviour and reproductive success of female Aedes aegypti mosquitoes, the main vector of dengue. Infection reduced survival to adulthood and increased adult female mosquito age-dependent mortality relative to uninfected individuals; this additional mortality was closely correlated with the number of parasite spores they harboured when they died. In the first gonotrophic cycle, infected females were less likely to blood-feed, took smaller meals when they did so, and developed fewer eggs than uninfected females. Even though the conditions of this laboratory study favoured minimal developmental times, the costs of infection were already being experienced by the time females reached an age at which they could first reproduce. These results suggest there will be selection pressure for mosquitoes to evolve resistance against this pathogen if it is used as an agent in a control program to reduce the transmission of mosquito-borne human diseases.

Potential novel risk factors for autochthonous and sylvatic transmission of human Chagas disease in the United States.

Chagas disease is an emerging vector-borne disease in the United States that causes progressive dilated cardiomyopathy in a third of infected humans. While transmission studies have been performed in Latin America, little is known about the source of infection in locally acquired cases in the United States. This letter describes the underlying factors possibly leading to an increased risk of disease transmission among high-risk groups in the United States.

Capacity of mosquitoes to transmit malaria depends on larval environment

Adult traits of holometabolous insects such as reproduction and survival can be shaped by conditions experienced during larval development. These “carry-over” effects influence not only individual life history and fitness, but can also impact interactions between insect hosts and parasites. Despite this, the implications of larval conditions for the transmission of human, wildlife and plant diseases that are vectored by insects remain poorly understood. We used Anopheles stephensi mosquitoes and the rodent malaria, Plasmodium yoelii yoelii, to investigate whether quality of larval habitat influenced vectorial capacity of adult mosquitoes. Larvae were reared under two dietary conditions; one group received a diet commonly used for colony maintenance (0.3 mg/individual/day of Tetrafin fish food) while the other group received a reduced food diet (0.1 mg/individual/day). Upon emergence, adults were provided an infectious blood feed. We assessed the effects of diet on a range of larval and adult traits including larval development times and survival, number of emerging adults, adult body size and survival, gonotrophic cycle length, and mating success. We also estimated the effects of larval diet on parasite infection rates and growth kinetics within the adult mosquitoes. Larval dietary regime affected larval survival and development, as well as size, reproductive success and survival of adult mosquitoes. Larval diet also affected the intensity of initial Plasmodium infection (oocyst stage) and parasite replication, but without differences in overall infection prevalence at either the oocyst or sporozoite stage. Together, the combined effects led to a relative reduction in vectorial capacity (a measure of the transmission potential of a mosquito population) in the low food treatment of 70%. This study highlights the need to consider environmental variation at the larval stages to better understand transmission dynamics and control of vector-borne diseases.

West Nile Fever - An Emerging And Re-Emerging Infectious Viral Metazoonosis

In recent years, many emerging and re-emerging zoonoses which resulted in high morbidity and mortality in humans and animals have attracted the attention of international and national authorities.Among several zoonotic diseases, West Nile fever is an important viral metazoonosis from public health and economic point of view. The disease is caused by West Nile virus which was first isolated from human blood in 1937 from Uganda. The virus is reported in humans and in a wide variety of animals including equines from many countries of world including India, Europe, Africa and USA. The bite of infected mosquitoes belonging to the genus Culex is the principal mode of disease transmission both in humans as well animals. Disease in man is characterized by fever, cephalalgia, pain in eyes, muscles and joints, lymphadenopathy, meningoencephalitis and maculopapular eruption mainly on trunk. Diagnosis of West Nile fever can be established by virus isolation from clinical materials and detection of virus specific antibodies in the serum of patients. RT-PCR can also be tried to make a rapid diagnosis. Since it is a metazoonosis, measures to control the mosquitoes, wearing protective clothing, and use of repellent cream will certainly reduce the incidence of West Nile fever. We are of the opinion that active surveillance of disease in humans, birds, animals, and vector (mosquito) is imperative to forecast emergence and re-emergence of this important viral metazoonosis. In addition, involvement of public health veterinarian in the control of zoonoses programme is also emphasized.

Prevalence of tick infestation in dromedary camels (Camelus dromedarius) brought for slaughter in Mashhad abattoir, Iran.

This study was carried out to investigate the prevalence of tick infestation and identify tick species that parasitize dromedary camels. Since April 2012 through March 2013, a total of 400 camels that brought for slaughter in Mashhad abattoir were examined for tick infestation. Out of the total 400 camels examined, 237 were infested and annual prevalence of tick infestation 59.25% (95% CI 54-64) was calculated. The higher prevalence rates were found in the summer and spring, especially the summer that prevalence rate was the highest. A total of 1,122 ticks were collected from the infested camels and identified by stereomicroscopy. Hyalomma dromedarii was the predominant tick species and comprised 70.76% of the collected ticks. The frequency of other species was as follows: H. excavatum (19.25%), H. anatolicum (4.81%), H. asiaticum (4.72%), Rhipicephalus turanicus (0.17%), H. detritum (0.09%), H. impeltatum (0.09%) and H. schulzei (0.09%). Based on the results of present study, it is concluded that camels mostly harbor Hyalomma spp. The species of this genus are the most notorious ticks for transmission of human and animal diseases. Therefore, appropriate tick control measures need to be employed and pour-on method for acaricide application is suggested because this method is fast, easy and suitable for use by camel owners in deserts.

Impact of global change on transmission of human infectious diseases.

Global change, which refers to large-scale changes in the earth system and human society, has been changing the outbreak and transmission mode of many infectious diseases. Climate change affects infectious diseases directly and indirectly. Meteorological factors including temperature, precipitation, humidity and radiation influence infectious disease by modulating pathogen, host and transmission pathways. Meteorological disasters such as droughts and floods directly impact the outbreak and transmission of infectious diseases. Climate change indirectly impacts infectious diseases by altering the ecological system, including its underlying surface and vegetation distribution. In addition, anthropogenic activities are a driving force for climate change and an indirect forcing of infectious disease transmission. International travel and rural-urban migration are a root cause of infectious disease transmission. Rapid urbanization along with poor infrastructure and high disease risk in the rural-urban fringe has been changing the pattern of disease outbreaks and mortality. Land use changes, such as agricultural expansion and deforestation, have already changed the transmission of infectious disease. Accelerated air, road and rail transportation development may not only increase the transmission speed of outbreaks, but also enlarge the scope of transmission area. In addition, more frequent trade and other economic activities will also increase the potential risks of disease outbreaks and facilitate the spread of infectious diseases.

Asparagine Substitution at PB2 Residue 701 Enhances the Replication, Pathogenicity, and Transmission of the 2009 Pandemic H1N1 Influenza A Virus

The 2009/2010 pandemic influenza virus (H1N1pdm) contains an avian-lineage PB2 gene that lacks E627K and D701N substitutions important in the pathogenesis and transmission of avian-origin viruses in humans or other mammals. Previous studies have shown that PB2-627K is not necessary because of a compensatory Q591R substitution. The role that PB2-701N plays in the H1N1pdm phenotype is not well understood. Therefore, PB2-D701N was introduced into an H1N1pdm virus (A/New York/1682/2009 (NY1682)) and analyzed in vitro and in vivo. Mini-genome replication assay, in vitro replication characteristics in cell lines, and analysis in the mouse and ferret models demonstrated that PB2-D701N increased virus replication rates and resulted in more severe pathogenicity in mice and more efficient transmission in ferrets. In addition, compared to the NY1682-WT virus, the NY1682-D701N mutant virus induced less IFN-λ and replicated to a higher titer in primary human alveolar epithelial cells. These findings suggest that the acquisition of the PB2-701N substitution by H1N1pdm viruses may result in more severe disease or increase transmission in humans.