scholarly journals Preadaptation of pandemic GII.4 noroviruses in unsampled virus reservoirs years before emergence

2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Christopher Ruis ◽  
Lisa C Lindesmith ◽  
Michael L Mallory ◽  
Paul D Brewer-Jensen ◽  
Josephine M Bryant ◽  
...  
Keyword(s):  
Strong Evidence ◽  
Host Population ◽  
Antigenic Drift ◽  
Genetic Changes ◽  
Pandemic Strain ◽  
Population Immunity ◽  
Virus Capsids ◽  
Global Spread ◽  
Ancestral Virus ◽  
Conventional Models

Abstract The control of re-occurring pandemic pathogens requires understanding the origins of new pandemic variants and the factors that drive their global spread. This is especially important for GII.4 norovirus, where vaccines under development offer promise to prevent hundreds of millions of annual gastroenteritis cases. Previous studies have hypothesized that new GII.4 pandemic viruses arise when previously circulating pandemic or pre-pandemic variants undergo substitutions in antigenic regions that enable evasion of host population immunity, as described by conventional models of antigenic drift. In contrast, we show here that the acquisition of new genetic and antigenic characteristics cannot be the proximal driver of new pandemics. Pandemic GII.4 viruses diversify and spread over wide geographical areas over several years prior to simultaneous pandemic emergence of multiple lineages, indicating that the necessary sequence changes must have occurred before diversification, years prior to pandemic emergence. We confirm this result through serological assays of reconstructed ancestral virus capsids, demonstrating that by 2003, the ancestral 2012 pandemic strain had already acquired the antigenic characteristics that allowed it to evade prevailing population immunity against the previous 2009 pandemic variant. These results provide strong evidence that viral genetic changes are necessary but not sufficient for GII.4 pandemic spread. Instead, we suggest that it is changes in host population immunity that enable pandemic spread of an antigenically preadapted GII.4 variant. These results indicate that predicting future GII.4 pandemic variants will require surveillance of currently unsampled reservoir populations. Furthermore, a broadly acting GII.4 vaccine will be critical to prevent future pandemics.

scholarly journals Preadaptation of pandemic GII.4 noroviruses in hidden virus reservoirs years before emergence

2019 ◽  
Author(s):  
Christopher Ruis ◽  
Lisa C. Lindesmith ◽  
Michael L. Mallory ◽  
Paul D. Brewer-Jensen ◽  
Josephine M. Bryant ◽  
...  
Keyword(s):  
Public Health ◽  
Vaccine Development ◽  
Host Population ◽  
Early Prediction ◽  
Economic Costs ◽  
Genetic Changes ◽  
Population Immunity ◽  
Global Spread ◽  
Serological Data ◽  
New Hypothesis

AbstractThe control of pandemic pathogens depends on early prediction of pandemic variants and, more generally, understanding origins of such variants and factors that drive their global spread. This is especially important for GII.4 norovirus, where vaccines under development offer promise to prevent hundreds of millions of annual gastroenteritis cases. Previous studies have suggested that new GII.4 pandemic viruses evolve from previous pandemic variants through substitutions in the antigenic region of the VP1 protein that enable evasion of host population immunity, leading to global spread. In contrast, we show here that the acquisition of new genetic and antigenic characteristics is not the proximal driver of new pandemics. Instead, pandemic GII.4 viruses circulate undetected for years before causing a new pandemic, during which time they diversify and spread over wide geographical areas. Serological data demonstrate that by 2003, some nine years before it emerged as a new pandemic, the ancestral 2012 pandemic strain had already acquired the antigenic characteristics that allowed it to evade prevailing population immunity against the previous 2009 pandemic variant. These results provide strong evidence that viral genetic changes are necessary but not sufficient for GII.4 pandemic spread. Instead, we suggest that it is changes in host population immunity that enable pandemic spread of an antigenically-preadapted GII.4 variant. These results indicate that predicting future GII.4 pandemic variants will require surveillance of currently unsampled reservoir populations. Furthermore, a broadly acting GII.4 vaccine will be critical to prevent future pandemics.SignificanceNorovirus pandemics and their associated public health and economic costs could be prevented by effective vaccines. However, vaccine development and distribution will require identification of the sources and drivers of new pandemics. We here use phylogenetics and serological experiments to develop and test a new hypothesis of pandemic norovirus emergence. We find that pandemic noroviruses preadapt, diversify and spread worldwide years prior to emergence, strongly indicating that genetic changes are necessary but not sufficient to drive a new pandemic. We instead suggest that changes in population immunity enable pandemic emergence of a pre-adapted low-level variant. These findings indicate that prediction of new pandemics will require surveillance of under-sampled virus reservoirs and that norovirus vaccines will need to elicit broad immunity.

scholarly journals From Protein to Pandemic: The Transdisciplinary Approach Needed to Prevent Spillover and the Next Pandemic

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1298
Author(s):  
Raina K. Plowright ◽  
Peter J. Hudson
Keyword(s):  
Immune Responses ◽  
Host Population ◽  
Reservoir Host ◽  
Innate Immune ◽  
Receptor Protein ◽  
The Novel ◽  
Innate Immune Responses ◽  
Transdisciplinary Approach ◽  
Sequence Of Events ◽  
Global Spread

Pandemics are a consequence of a series of processes that span scales from viral biology at 10−9 m to global transmission at 106 m. The pathogen passes from one host species to another through a sequence of events that starts with an infected reservoir host and entails interspecific contact, innate immune responses, receptor protein structure within the potential host, and the global spread of the novel pathogen through the naive host population. Each event presents a potential barrier to the onward passage of the virus and should be characterized with an integrated transdisciplinary approach. Epidemic control is based on the prevention of exposure, infection, and disease. However, the ultimate pandemic prevention is prevention of the spillover event itself. Here, we focus on the potential for preventing the spillover of henipaviruses, a group of viruses derived from bats that frequently cross species barriers, incur high human mortality, and are transmitted among humans via stuttering chains. We outline the transdisciplinary approach needed to prevent the spillover process and, therefore, future pandemics.

scholarly journals Genomic stability among O3:K6 V. parahaemolyticus pandemic strains isolated between 1996 to 2012 in American countries

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Abraham Guerrero ◽  
Bruno Gomez-Gil ◽  
Marcial Leonardo Lizarraga-Partida
Keyword(s):  
Reference Strain ◽  
Genomic Stability ◽  
Gastrointestinal Illness ◽  
Reference Sequence ◽  
Aquatic Habitats ◽  
Genetic Changes ◽  
Pandemic Strain ◽  
Toxigenic Strains ◽  
Pandemic Strains ◽  
High Level

Abstract Background The V. parahaemolyticus pandemic clone, results in the development of gastrointestinal illness in humans. Toxigenic strains of this species are frequently isolated from aquatic habitats and organisms such as mollusks and crustaceans. Reports on the isolation of the pandemic clone started in 1996, when a new O3:K6 clone was identified in Asia, that rapidly spread worldwide, becoming the predominant clone isolated from clinical cases. In this study whole genome sequencing was accomplished with an Illumina MiniSeq platform, upon six novel V. parahaemolyticus strains, that have been isolated in Mexico since 1998 and three representative genomes of strains that were isolated from reported outbreaks in other American countries, and were deposited in the GenBank. These nine genomes were compared against the reference sequence of the O3:K6 pandemic strain (RIMD 2210633), which was isolated in 1996, to determine sequence differences within American isolates and between years of isolation. Results The results indicated that strains that were isolated at different times and from different countries, were highly genetically similar, among them as well as to the reference strain RIMD 2210633, indicating a high level of genetic stability among the strains from American countries between 1996 to 2012, without significant genetic changes relative to the reference strain RIMD 2210633, which was isolated in 1996 and was considered to be representative of a novel O3:K6 pandemic strain. Conclusions The genomes of V. parahaemolyticus strains isolated from clinical and environmental sources in Mexico and other American countries, presented common characteristics that have been reported for RIMD 2210633 O3:K6 pandemic strain. The major variations that were registered in this study corresponded to genes non associated to virulence factors, which could be the result of adaptations to different environmental conditions. Nevertheless, results do not show a clear pattern with the year or locality where the strains were isolated, which is an indication of a genomic stability of the studied strains.

Sexually Transmitted, Urinary Tract, and Gastrointestinal Tract Infections

2016 ◽  
pp. 521-538
Author(s):  
M. Rizwan Sohail
Keyword(s):  
Influenza A ◽  
The United States ◽  
Antigenic Drift ◽  
Influenza B ◽  
Sexually Transmitted ◽  
Influenza Pandemics ◽  
Population Immunity ◽  
Large Numbers ◽  
Seasonal Epidemics ◽  
Tract Infections

Influenza causes annual, seasonal epidemics that lead to tens of thousands of deaths each year in the United States. Two influenza A strains (H3N2 and H1N1) and 1 or 2 influenza B strains typically circulate during winter months and undergo minor antigenic mutations (antigenic drift) resulting in annual seasonal epidemics. Influenza pandemics occur more rarely (every 20-30 years) and are the result of major antigenic changes (antigenic shift) leading to large numbers of infections due to low levels of population immunity. In seasonal epidemics, 80% to 90% of deaths due to influenza occur in persons older than 65 years.

scholarly journals Phenotypic differences in viral immune escape explained by linking within-host dynamics to host-population immunity

2010 ◽  
Vol 265 (4) ◽  
pp. 501-510 ◽  
Author(s):  
K.M. Pepin ◽  
I. Volkov ◽  
J.R. Banavar ◽  
C.O. Wilke ◽  
B.T. Grenfell
Keyword(s):  
Immune Escape ◽  
Host Population ◽  
Phenotypic Differences ◽  
Population Immunity

scholarly journals Evidence for adaptive evolution in the receptor-binding domain of seasonal coronaviruses OC43 and 229e

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Kathryn E Kistler ◽  
Trevor Bedford
Keyword(s):  
Adaptive Evolution ◽  
Immune Evasion ◽  
Human Population ◽  
Seasonal Influenza ◽  
Respiratory Infections ◽  
Antigenic Drift ◽  
Spike Protein ◽  
Immune Memory ◽  
Receptor Binding Domain ◽  
Genetic Changes

Seasonal coronaviruses (OC43, 229E, NL63, and HKU1) are endemic to the human population, regularly infecting and reinfecting humans while typically causing asymptomatic to mild respiratory infections. It is not known to what extent reinfection by these viruses is due to waning immune memory or antigenic drift of the viruses. Here we address the influence of antigenic drift on immune evasion of seasonal coronaviruses. We provide evidence that at least two of these viruses, OC43 and 229E, are undergoing adaptive evolution in regions of the viral spike protein that are exposed to human humoral immunity. This suggests that reinfection may be due, in part, to positively selected genetic changes in these viruses that enable them to escape recognition by the immune system. It is possible that, as with seasonal influenza, these adaptive changes in antigenic regions of the virus would necessitate continual reformulation of a vaccine made against them.

scholarly journals ‘Dark matter’, second waves and epidemiological modelling

2020 ◽  
Vol 5 (12) ◽  
pp. e003978
Author(s):  
Karl Friston ◽  
Anthony Costello ◽  
Deenan Pillay
Keyword(s):  
Bayesian Model ◽  
Model Comparison ◽  
Herd Immunity ◽  
Population Immunity ◽  
Bayesian Model Comparison ◽  
Overwhelming Evidence ◽  
The Usa ◽  
Conventional Models ◽  
Support Programmes ◽  
The Uk

Recent reports using conventional Susceptible, Exposed, Infected and Removed models suggest that the next wave of the COVID-19 pandemic in the UK could overwhelm health services, with fatalities exceeding the first wave. We used Bayesian model comparison to revisit these conclusions, allowing for heterogeneity of exposure, susceptibility and transmission. We used dynamic causal modelling to estimate the evidence for alternative models of daily cases and deaths from the USA, the UK, Brazil, Italy, France, Spain, Mexico, Belgium, Germany and Canada over the period 25 January 2020 to 15 June 2020. These data were used to estimate the proportions of people (i) not exposed to the virus, (ii) not susceptible to infection when exposed and (iii) not infectious when susceptible to infection. Bayesian model comparison furnished overwhelming evidence for heterogeneity of exposure, susceptibility and transmission. Furthermore, both lockdown and the build-up of population immunity contributed to viral transmission in all but one country. Small variations in heterogeneity were sufficient to explain large differences in mortality rates. The best model of UK data predicts a second surge of fatalities will be much less than the first peak. The size of the second wave depends sensitively on the loss of immunity and the efficacy of Find-Test-Trace-Isolate-Support programmes. In summary, accounting for heterogeneity of exposure, susceptibility and transmission suggests that the next wave of the SARS-CoV-2 pandemic will be much smaller than conventional models predict, with less economic and health disruption. This heterogeneity means that seroprevalence underestimates effective herd immunity and, crucially, the potential of public health programmes.

scholarly journals Influenza A H1N1 Pandemic Strain Evolution – Divergence and the Potential for Antigenic Drift Variants

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e93632 ◽  
Author(s):  
Eili Y. Klein ◽  
Adrian W. R. Serohijos ◽  
Jeong-Mo Choi ◽  
Eugene I. Shakhnovich ◽  
Andrew Pekosz
Keyword(s):  
Influenza A ◽  
Antigenic Drift ◽  
H1n1 Pandemic ◽  
Pandemic Strain ◽  
Strain Evolution ◽  
Influenza A H1n1

scholarly journals Adaptation of tobacco etch potyvirus to a susceptible ecotype of Arabidopsis thaliana capacitates it for systemic infection of resistant ecotypes

2010 ◽  
Vol 365 (1548) ◽  
pp. 1997-2007 ◽  
Author(s):  
Jasna Lalić ◽  
Patricia Agudelo-Romero ◽  
Purificación Carrasco ◽  
Santiago F. Elena
Keyword(s):  
Systemic Infection ◽  
Host Population ◽  
Genetic Constitution ◽  
Viral Pathogens ◽  
Virus Diversity ◽  
Rapid Spread ◽  
Emerging Virus ◽  
Ancestral Virus ◽  
Empirical Tests ◽  
Tobacco Etch Potyvirus

Viral pathogens continue to emerge among humans, domesticated animals and cultivated crops. The existence of genetic variance for resistance in the host population is crucial to the spread of an emerging virus. Models predict that rapid spread decreases with the frequency and diversity of resistance alleles in the host population. However, empirical tests of this hypothesis are scarce. Arabiodpsis thaliana —tobacco etch potyvirus (TEV) provides an experimentally suitable pathosystem to explore the interplay between genetic variation in host's susceptibility and virus diversity. Systemic infection of A. thaliana with TEV is controlled by three dominant loci, with different ecotypes varying in susceptibility depending on the genetic constitution at these three loci. Here, we show that the TEV adaptation to a susceptible ecotype allowed the virus to successfully infect, replicate and induce symptoms in ecotypes that were fully resistant to the ancestral virus. The value of these results is twofold. First, we showed that the existence of partially susceptible individuals allows for the emerging virus to bypass resistance alleles that the virus has never encountered. Second, the concept of resistance genes may only be valid for a well-defined viral genotype but not for polymorphic viral populations.

scholarly journals The canine distemper epidemic in Serengeti: are lions victims of a new highly virulent canine distemper virus strain, or is pathogen circulation stochasticity to blame?

2007 ◽  
Vol 4 (17) ◽  
pp. 1127-1134 ◽  
Author(s):  
Micheline Guiserix ◽  
Narges Bahi-Jaber ◽  
David Fouchet ◽  
Frank Sauvage ◽  
Dominique Pontier
Keyword(s):  
Virus Transmission ◽  
Host Population ◽  
Disease Emergence ◽  
Canine Distemper ◽  
Population Immunity ◽  
Stochastic Fluctuations ◽  
Low Probability ◽  
Highly Virulent ◽  
Canine Distemper Virus Strain ◽  
Made In

In the year 1994, the Serengeti lion population was decimated by a canine distemper disease outbreak. Retrospective investigations showed that this host population had already been in contact with the pathogen in 1981 without any detected sign of disease. As an alternative to the virus mutation hypothesis to explain this difference in virulences observed in 1981 and 1994, we propose a novel mechanism of disease emergence based on variation in population immunity. We use a stochastic model to show that stochastic fluctuations in pathogen circulation, owing to a low probability of virus transmission from its reservoir to the target host and thereby resulting in variations in the global immunity level of the target host population, can explain the observations made in Serengeti. This mechanism may also be involved in other infectious disease emergences or re-emergences.

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