scholarly journals Onward transmission of viruses: how do viruses emerge to cause epidemics after spillover?

2019 ◽  
Vol 374 (1782) ◽  
pp. 20190017 ◽  
Author(s):  
Brian R. Wasik ◽  
Emmie de Wit ◽  
Vincent Munster ◽  
James O. Lloyd-Smith ◽  
Luis Martinez-Sobrido ◽  
...  
Keyword(s):  
Influenza A ◽  
Host Population ◽  
Initial Population ◽  
Influenza A Viruses ◽  
Theme Issue ◽  
New Host ◽  
Viral Pathogen ◽  
Efficient Replication ◽  
New Hosts ◽  
Efficient Transmission

The critical step in the emergence of a new epidemic or pandemic viral pathogen occurs after it infects the initial spillover host and then is successfully transmitted onwards, causing an outbreak chain of transmission within that new host population. Crossing these choke points sets a pathogen on the pathway to epidemic emergence. While many viruses spill over to infect new or alternative hosts, only a few accomplish this transition—and the reasons for the success of those pathogens are still unclear. Here, we consider this issue related to the emergence of animal viruses, where factors involved likely include the ability to efficiently infect the new animal host, the demographic features of the initial population that favour onward transmission, the level of shedding and degree of susceptibility of individuals of that population, along with pathogen evolution favouring increased replication and more efficient transmission among the new host individuals. A related form of emergence involves mutations that increased spread or virulence of an already-known virus within its usual host. In all of these cases, emergence may be due to altered viral properties, changes in the size or structure of the host populations, ease of transport, climate change or, in the case of arboviruses, to the expansion of the arthropod vectors. Here, we focus on three examples of viruses that have gained efficient onward transmission after spillover: influenza A viruses that are respiratory transmitted, HIV, a retrovirus, that is mostly blood or mucosal transmitted, and canine parvovirus that is faecal:oral transmitted. We describe our current understanding of the changes in the viruses that allowed them to overcome the barriers that prevented efficient replication and spread in their new hosts. We also briefly outline how we could gain a better understanding of the mechanisms and variability in order to better anticipate these events in the future. This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.

scholarly journals Viral Factors Important for Efficient Replication of Influenza A Viruses in Cells of the Central Nervous System

2019 ◽  
Vol 93 (11) ◽  
Author(s):  
Jurre Y. Siegers ◽  
Marco W. G. van de Bildt ◽  
Zhanmin Lin ◽  
Lonneke M. Leijten ◽  
Rémon A. M. Lavrijssen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Influenza A ◽  
H5n1 Virus ◽  
Influenza Viruses ◽  
Virus Infections ◽  
Influenza A Viruses ◽  
Cns Disease ◽  
Efficient Replication ◽  
Hpai H5n1 ◽  
In Cells

ABSTRACTCentral nervous system (CNS) disease is one of the most common extrarespiratory tract complications of influenza A virus infections. Remarkably, zoonotic H5N1 virus infections are more frequently associated with CNS disease than seasonal or pandemic influenza viruses. Little is known about the interaction between influenza A viruses and cells of the CNS; therefore, it is currently unknown which viral factors are important for efficient replication. Here, we determined the replication kinetics of a seasonal, pandemic, zoonotic, and lab-adapted influenza A virus in human neuron-like (SK-N-SH) and astrocyte-like (U87-MG) cells and primary mouse cortex neurons. In general, highly pathogenic avian influenza (HPAI) H5N1 virus replicated most efficiently in all cells, which was associated with efficient attachment and infection. Seasonal H3N2 and to a lesser extent pandemic H1N1 virus replicated in a trypsin-dependent manner in SK-N-SH but not in U87-MG cells. In the absence of trypsin, only HPAI H5N1 and WSN viruses replicated. Removal of the multibasic cleavage site (MBCS) from HPAI H5N1 virus attenuated, but did not abrogate, replication. Taken together, our results showed that the MBCS and, to a lesser extent, the ability to attach are important determinants for efficient replication of HPAI H5N1 virus in cells of the CNS. This suggests that both an alternative hemagglutinin (HA) cleavage mechanism and preference for α-2,3-linked sialic acids allowing efficient attachment contribute to the ability of influenza A viruses to replicate efficiently in cells of the CNS. This study further improves our knowledge on potential viral factors important for the neurotropic potential of influenza A viruses.IMPORTANCECentral nervous system (CNS) disease is one of the most common extrarespiratory tract complications of influenza A virus infections, and the frequency and severity differ between seasonal, pandemic, and zoonotic influenza viruses. However, little is known about the interaction of these viruses with cells of the CNS. Differences among seasonal, pandemic, and zoonotic influenza viruses in replication efficacy in CNS cells,in vitro, suggest that the presence of an alternative HA cleavage mechanism and ability to attach are important viral factors. Identifying these viral factors and detailed knowledge of the interaction between influenza virus and CNS cells are important to prevent and treat this potentially lethal CNS disease.

scholarly journals CRK adaptor protein expression is required for efficient replication of avian influenza A viruses and controls JNK-mediated apoptotic responses

2010 ◽  
Vol 12 (6) ◽  
pp. 831-843 ◽  
Author(s):  
Eike R. Hrincius ◽  
Viktor Wixler ◽  
Thorsten Wolff ◽  
Ralf Wagner ◽  
Stephan Ludwig ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Protein Expression ◽  
Influenza A ◽  
Adaptor Protein ◽  
Influenza A Viruses ◽  
Efficient Replication

scholarly journals Evidence for Avian and Human Host Cell Factors That Affect the Activity of Influenza Virus Polymerase

2010 ◽  
Vol 84 (19) ◽  
pp. 9978-9986 ◽  
Author(s):  
Olivier Moncorgé ◽  
Manuela Mura ◽  
Wendy S. Barclay
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Host Range ◽  
Influenza A ◽  
Human Cells ◽  
Influenza A Viruses ◽  
New Host ◽  
Range Restriction ◽  
Positive Factor

ABSTRACT Typical avian influenza A viruses do not replicate efficiently in humans. The molecular basis of host range restriction and adaptation of avian influenza A viruses to a new host species is still not completely understood. Genetic determinants of host range adaptation have been found on the polymerase complex (PB1, PB2, and PA) as well as on the nucleoprotein (NP). These four viral proteins constitute the minimal set for transcription and replication of influenza viral RNA. It is widely documented that in human cells, avian-derived influenza A viral polymerase is poorly active, but despite extensive study, the reason for this blockade is not known. We monitored the activity of influenza A viral polymerases in heterokaryons formed between avian (DF1) and human (293T) cells. We have discovered that a positive factor present in avian cells enhances the activity of the avian influenza virus polymerase. We found no evidence for the existence of an inhibitory factor for avian virus polymerase in human cells, and we suggest, instead, that the restriction of avian influenza virus polymerases in human cells is the consequence of the absence or the low expression of a compatible positive cofactor. Finally, our results strongly suggest that the well-known adaptative mutation E627K on viral protein PB2 facilitates the ability of a human positive factor to enhance replication of influenza virus in human cells.

scholarly journals Cross-Species Virus Transmission and the Emergence of New Epidemic Diseases

2008 ◽  
Vol 72 (3) ◽  
pp. 457-470 ◽  
Author(s):  
Colin R. Parrish ◽  
Edward C. Holmes ◽  
David M. Morens ◽  
Eun-Chung Park ◽  
Donald S. Burke ◽  
...  
Keyword(s):  
Host Range ◽  
Virus Transmission ◽  
Host Population ◽  
Evolutionary Mechanisms ◽  
New Host ◽  
Transmission Cycle ◽  
Host Interactions ◽  
Natural Hosts ◽  
New Hosts ◽  
Host Infection

SUMMARY Host range is a viral property reflecting natural hosts that are infected either as part of a principal transmission cycle or, less commonly, as “spillover” infections into alternative hosts. Rarely, viruses gain the ability to spread efficiently within a new host that was not previously exposed or susceptible. These transfers involve either increased exposure or the acquisition of variations that allow them to overcome barriers to infection of the new hosts. In these cases, devastating outbreaks can result. Steps involved in transfers of viruses to new hosts include contact between the virus and the host, infection of an initial individual leading to amplification and an outbreak, and the generation within the original or new host of viral variants that have the ability to spread efficiently between individuals in populations of the new host. Here we review what is known about host switching leading to viral emergence from known examples, considering the evolutionary mechanisms, virus-host interactions, host range barriers to infection, and processes that allow efficient host-to-host transmission in the new host population.

Influenza A virus transmission: contributing factors and clinical implications

2010 ◽  
Vol 12 ◽  
Author(s):  
Jessica A. Belser ◽  
Taronna R. Maines ◽  
Terrence M. Tumpey ◽  
Jacqueline M. Katz
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Influenza A ◽  
Severe Disease ◽  
Virus Transmission ◽  
Influenza Viruses ◽  
Clinical Implications ◽  
Influenza A Viruses ◽  
Molecular Features ◽  
Efficient Transmission

Efficient human-to-human transmission is a necessary property for the generation of a pandemic influenza virus. To date, only influenza A viruses within the H1–H3 subtypes have achieved this capacity. However, sporadic cases of severe disease in individuals following infection with avian influenza A viruses over the past decade, and the emergence of a pandemic H1N1 swine-origin virus in 2009, underscore the need to better understand how influenza viruses acquire the ability to transmit efficiently. In this review, we discuss the biological constraints and molecular features known to affect virus transmissibility to and among humans. Factors influencing the behaviour of aerosols in the environment are described, and the mammalian models used to study virus transmission are presented. Recent progress in understanding the molecular determinants that confer efficient transmission has identified crucial roles for the haemagglutinin and polymerase proteins; nevertheless, influenza virus transmission remains a polygenic trait that is not completely understood. The clinical implications of this research, including methods currently under investigation to mitigate influenza virus human-to-human transmission, are discussed. A better understanding of the viral determinants necessary for efficient transmission will allow us to identify avian influenza viruses with pandemic potential.

scholarly journals Mucin-mimetic glycan arrays integrating machine learning for analyzing receptor pattern recognition by influenza A viruses

2021 ◽  
Author(s):  
Taryn M. Lucas ◽  
Chitrak Gupta ◽  
Meghan O. Altman ◽  
Emi Sanchez ◽  
Matthew R. Naticchia ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Mammalian Cells ◽  
Influenza A ◽  
Learning Algorithm ◽  
Sialic Acids ◽  
Soluble Form ◽  
Support Vector ◽  
Glycan Array ◽  
Influenza A Viruses ◽  
New Host

ABSTRACTInfluenza A viruses (IAVs) exploit host glycans in airway epithelial mucosa to gain entry and initiate infection. Rapid detection of changes in IAV specificity towards host glycan classes can provide early indication of virus transmissibility and infection potential. IAVs use hemagglutinins (HA) to bind sialic acids linked to larger glycan structures and a switch in HA specificity from α2,3-to α2,6-linked sialoglycans is considered a prerequisite for viral transmission from birds to humans. While the changes in HA structure associated with the evolution of binding phenotype have been mapped, the influence of glycan receptor presentation on IAV specificity remains obscured. Here, we describe a glycan array platform which uses synthetic mimetics of mucin glycoproteins to model how receptor presentation in the mucinous glycocalyx, including glycan type and valency of the glycoconjugates and their surface density, impact IAV binding. We found that H1N1 virus produced in embryonated chicken eggs, which recognizes both receptor types, exclusively engaged mucin-mimetics carrying α2,3-linked sialic acids in their soluble form. The virus was able utilize both receptor structures when the probes were immobilized on the array; however, increasing density in the mucin-mimetic brush diminished viral adhesion. Propagation in mammalian cells produced a change in receptor pattern recognition by the virus, without altering its HA affinity, toward improved binding of α2,6-sialylated mucin mimetics and reduced sensitivity to surface crowding of the probes. Application of a support vector machine (SVM) learning algorithm as part of the glycan array binding analysis efficiently characterized this shift in binding preference and may prove useful to study the evolution of viral responses to a new host.

scholarly journals Zoonotic Potential of Currently Circulating Avian Influenza Viruses

2020 ◽  
Vol 39 (1) ◽  
pp. 8-14
Author(s):  
Vladimir Savić
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
Human Infection ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Avian Influenza Viruses ◽  
Influenza Pandemics ◽  
Human Infections ◽  
Virus Adaptation ◽  
Efficient Transmission

Over the past and the current centuries, human influenza pandemics have been attributable to viruses with an avian ancestry. Birds are the main source of influenza A viruses and harbour a variety of antigenic subtypes. Certain avian influenza viruses are capable for cross-species transmission including human infections. Although sustained intrehuman transmission of such viruses has not been documented so far, each human infection with avian influenza viruses provides chances for the virus adaptation towards efficient transmission within human population. Here are reviewed currently circulating avian influenza viruses that are of major significance for public health.

scholarly journals Sulfatide Is Required for Efficient Replication of Influenza A Virus

2008 ◽  
Vol 82 (12) ◽  
pp. 5940-5950 ◽  
Author(s):  
Tadanobu Takahashi ◽  
Kouki Murakami ◽  
Momoe Nagakura ◽  
Hideyuki Kishita ◽  
Shinya Watanabe ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Influenza A ◽  
H1n1 Virus ◽  
Therapeutic Strategies ◽  
Arylsulfatase A ◽  
Influenza A Viruses ◽  
Lethal Challenge ◽  
Ribonucleoprotein Complexes ◽  
Efficient Replication ◽  
Infected Cells

ABSTRACT Sulfatide is abundantly expressed in various mammalian organs, including the intestines and trachea, in which influenza A viruses (IAVs) replicate. However, the function of sulfatide in IAV infection remains unknown. Sulfatide is synthesized by two transferases, ceramide galactosyltransferase (CGT) and cerebroside sulfotransferase (CST), and is degraded by arylsulfatase A (ASA). In this study, we demonstrated that sulfatide enhanced IAV replication through efficient translocation of the newly synthesized IAV nucleoprotein (NP) from the nucleus to the cytoplasm, by using genetically produced cells in which sulfatide expression was down-regulated by RNA interference against CST mRNA or overexpression of the ASA gene and in which sulfatide expression was up-regulated by overexpression of both the CST and CGT genes. Treatment of IAV-infected cells with an antisulfatide monoclonal antibody (MAb) or an anti-hemagglutinin (HA) MAb, which blocks the binding of IAV and sulfatide, resulted in a significant reduction in IAV replication and accumulation of the viral NP in the nucleus. Furthermore, antisulfatide MAb protected mice against lethal challenge with pathogenic influenza A/WSN/33 (H1N1) virus. These results indicate that association of sulfatide with HA delivered to the cell surface induces translocation of the newly synthesized IAV ribonucleoprotein complexes from the nucleus to the cytoplasm. Our findings provide new insights into IAV replication and suggest new therapeutic strategies.

scholarly journals The Critical Interspecies Transmission Barrier at the Animal–Human Interface

2019 ◽  
Vol 4 (2) ◽  
pp. 72 ◽  
Author(s):  
Subbarao
Keyword(s):  
Influenza A ◽  
Influenza Pandemic ◽  
Interspecies Transmission ◽  
Small Subset ◽  
Influenza A Viruses ◽  
Species Barrier ◽  
New Host ◽  
Human Interface ◽  
Wide Range ◽  
Reservoir Hosts

Influenza A viruses (IAVs) infect humans and a wide range of animal species in nature, and waterfowl and shorebirds are their reservoir hosts. Of the 18 haemagglutinin (HA) and 11 neuraminidase (NA) subtypes of IAV, 16 HA and 9 NA subtypes infect aquatic birds. However, among the diverse pool of IAVs in nature, only a limited number of animal IAVs cross the species barrier to infect humans and a small subset of those have spread efficiently from person to person to cause an influenza pandemic. The ability to infect a different species, replicate in the new host and transmit are three distinct steps in this process. Viral and host factors that are critical determinants of the ability of an avian IAV to infect and spread in humans are discussed.

scholarly journals HA stabilization promotes replication and transmission of swine H1N1 gamma influenza viruses in ferrets

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Meng Hu ◽  
Guohua Yang ◽  
Jennifer DeBeauchamp ◽  
Jeri Carol Crumpton ◽  
Hyunsuh Kim ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Mammalian Cells ◽  
Influenza A ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Airborne Transmission ◽  
Efficient Replication ◽  
Ha Protein ◽  
Receptor Binding Specificity

Pandemic influenza A viruses can emerge from swine, an intermediate host that supports adaptation of human-preferred receptor-binding specificity by the hemagglutinin (HA) surface antigen. Other HA traits necessary for pandemic potential are poorly understood. For swine influenza viruses isolated in 2009–2016, gamma-clade viruses had less stable HA proteins (activation pH 5.5–5.9) than pandemic clade (pH 5.0–5.5). Gamma-clade viruses replicated to higher levels in mammalian cells than pandemic clade. In ferrets, a model for human adaptation, a relatively stable HA protein (pH 5.5–5.6) was necessary for efficient replication and airborne transmission. The overall airborne transmission frequency in ferrets for four isolates tested was 42%, and isolate G15 airborne transmitted 100% after selection of a variant with a stabilized HA. The results suggest swine influenza viruses containing both a stabilized HA and alpha-2,6 receptor binding in tandem pose greater pandemic risk. Increasing evidence supports adding HA stability to pre-pandemic risk assessment algorithms.

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