scholarly journals Causes and Consequences of Spatial Within-Host Viral Spread

Viruses ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 627 ◽  
Author(s):  
Molly Gallagher ◽  
Christopher Brooke ◽  
Ruian Ke ◽  
Katia Koelle
Keyword(s):  
Influenza A ◽  
Current Knowledge ◽  
Control Strategies ◽  
Experimental Studies ◽  
Spatial Dynamics ◽  
Spatial Process ◽  
Influenza A Viruses ◽  
Long Distance ◽  
Viral Spread ◽  
Shed Light

The spread of viral pathogens both between and within hosts is inherently a spatial process. While the spatial aspects of viral spread at the epidemiological level have been increasingly well characterized, the spatial aspects of viral spread within infected hosts are still understudied. Here, with a focus on influenza A viruses (IAVs), we first review experimental studies that have shed light on the mechanisms and spatial dynamics of viral spread within hosts. These studies provide strong empirical evidence for highly localized IAV spread within hosts. Since mathematical and computational within-host models have been increasingly used to gain a quantitative understanding of observed viral dynamic patterns, we then review the (relatively few) computational modeling studies that have shed light on possible factors that structure the dynamics of spatial within-host IAV spread. These factors include the dispersal distance of virions, the localization of the immune response, and heterogeneity in host cell phenotypes across the respiratory tract. While informative, we find in these studies a striking absence of theoretical expectations of how spatial dynamics may impact the dynamics of viral populations. To mitigate this, we turn to the extensive ecological and evolutionary literature on range expansions to provide informed theoretical expectations. We find that factors such as the type of density dependence, the frequency of long-distance dispersal, specific life history characteristics, and the extent of spatial heterogeneity are critical factors affecting the speed of population spread and the genetic composition of spatially expanding populations. For each factor that we identified in the theoretical literature, we draw parallels to its analog in viral populations. We end by discussing current knowledge gaps related to the spatial component of within-host IAV spread and the potential for within-host spatial considerations to inform the development of disease control strategies.

scholarly journals Causes and Consequences of Spatial Within-Host Viral Spread

2018 ◽  
Author(s):  
Molly E. Gallagher ◽  
Christopher B. Brooke ◽  
Ruian Ke ◽  
Katia Koelle
Keyword(s):  
Influenza Virus ◽  
Computational Modeling ◽  
Current Knowledge ◽  
Control Strategies ◽  
Experimental Studies ◽  
Spatial Dynamics ◽  
Spatial Process ◽  
Spatial Spread ◽  
Viral Spread ◽  
Modeling Studies

The spread of viral pathogens both between and within hosts is inherently a spatial process. While the spatial aspects of viral spread at the epidemiological level have been increasingly well characterized, the spatial aspects of viral spread within infected hosts are still understudied. Recent experimental studies, however, have started to shed more light on the mechanisms and spatial dynamics of viral spread within hosts. Here, we review these experimental studies as well as the limited number of computational modeling efforts that have begun to integrate spatial considerations for understanding within-host viral spread. We limit our review to influenza virus to highlight key mechanisms affecting spatial aspects of viral spread for pathogens of the respiratory tract. There is considerable empirical evidence for highly spatial within-host spread of influenza virus, yet few computational modeling studies that shed light on possible factors that structure the dynamics of this spatial spread. In existing modeling studies, there is also a striking absence of theoretical expectations of how spatial dynamics may impact the dynamics of viral populations. To mitigate this, we turn to the extensive ecological and evolutionary literature to provide informed theoretical expectations for what viral and host factors may impact the spatial patterns of within-host viral dynamics and for how spatial spread will affect the genetic composition of within-host viral populations. We end by discussing current knowledge gaps related to the spatial component of within-host influenza virus spread and the potential for within-host spatial considerations to inform the development of disease control strategies.

Avian Influenza Human Infections at the Human-Animal Interface

2020 ◽  
Vol 222 (4) ◽  
pp. 528-537 ◽  
Author(s):  
Damien A M Philippon ◽  
Peng Wu ◽  
Benjamin J Cowling ◽  
Eric H Y Lau
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
Control Strategies ◽  
Influenza Pandemic ◽  
World Health ◽  
Emerging Pathogens ◽  
Influenza A Viruses ◽  
Dead Bird ◽  
Risk Of Death ◽  
Human Infections

Abstract Background Avian influenza A viruses (AIVs) are among the most concerning emerging and re-emerging pathogens because of the potential risk for causing an influenza pandemic with catastrophic impact. The recent increase in domestic animals and poultry worldwide was followed by an increase of human AIV outbreaks reported. Methods We reviewed the epidemiology of human infections with AIV from the literature including reports from the World Health Organization, extracting information on virus subtype, time, location, age, sex, outcome, and exposure. Results We described the characteristics of more than 2500 laboratory-confirmed human infections with AIVs. Human infections with H5N1 and H7N9 were more frequently reported than other subtypes. Risk of death was highest among reported cases infected with H5N1, H5N6, H7N9, and H10N8 infections. Older people and males tended to have a lower risk of infection with most AIV subtypes, except for H7N9. Visiting live poultry markets was mostly reported by H7N9, H5N6, and H10N8 cases, while exposure to sick or dead bird was mostly reported by H5N1, H7N2, H7N3, H7N4, H7N7, and H10N7 cases. Conclusions Understanding the profile of human cases of different AIV subtypes would guide control strategies. Continued monitoring of human infections with AIVs is essential for pandemic preparedness.

scholarly journals Influenza Viruses and mRNA Splicing: Doing More with Less

mBio ◽  
2014 ◽  
Vol 5 (3) ◽  
Author(s):  
Julia Dubois ◽  
Olivier Terrier ◽  
Manuel Rosa-Calatrava
Keyword(s):  
Influenza A ◽  
Current Knowledge ◽  
Influenza Viruses ◽  
Splicing Regulation ◽  
Influenza A Viruses ◽  
Sequence Alignments ◽  
Cellular Expression ◽  
Replication Stage ◽  
Regulation Mechanisms ◽  
Splicing Machinery

ABSTRACTDuring their nuclear replication stage, influenza viruses hijack the host splicing machinery to process some of their RNA segments, the M and NS segments. In this review, we provide an overview of the current knowledge gathered on this interplay between influenza viruses and the cellular spliceosome, with a particular focus on influenza A viruses (IAV). These viruses have developed accurate regulation mechanisms to reassign the host spliceosome to alter host cellular expression and enable an optimal expression of specific spliced viral products throughout infection. Moreover, IAV segments undergoing splicing display high levels of similarity with human consensus splice sites and their viral transcripts show noteworthy secondary structures. Sequence alignments and consensus analyses, along with recently published studies, suggest both conservation and evolution of viral splice site sequences and structure for improved adaptation to the host. Altogether, these results emphasize the ability of IAV to be well adapted to the host’s splicing machinery, and further investigations may contribute to a better understanding of splicing regulation with regard to viral replication, host range, and pathogenesis.

scholarly journals Influenza–Host Interplay and Strategies for Universal Vaccine Development

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 548
Author(s):  
Hye Suk Hwang ◽  
Mincheol Chang ◽  
Yoong Ahm Kim
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Vaccine Development ◽  
Current Knowledge ◽  
Host Cells ◽  
Influenza A Viruses ◽  
Universal Vaccine ◽  
Lectin Receptors ◽  
Endosomal Membrane ◽  
Influenza Virus Hemagglutinin

Influenza is an annual epidemic and an occasional pandemic caused by pathogens that are responsible for infectious respiratory disease. Humans are highly susceptible to the infection mediated by influenza A viruses (IAV). The entry of the virus is mediated by the influenza virus hemagglutinin (HA) glycoprotein that binds to the cellular sialic acid receptors and facilitates the fusion of the viral membrane with the endosomal membrane. During IAV infection, virus-derived pathogen-associated molecular patterns (PAMPs) are recognized by host intracellular specific sensors including toll-like receptors (TLRs), C-type lectin receptors, retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) either on the cell surface or intracellularly in endosomes. Herein, we comprehensively review the current knowledge available on the entry of the influenza virus into host cells and the molecular details of the influenza virus–host interface. We also highlight certain strategies for the development of universal influenza vaccines.

scholarly journals Replication competent, 10-segmented influenza viruses as antiviral therapeutics

2019 ◽  
Author(s):  
Griffin D. Haas ◽  
Alfred T. Harding ◽  
Nicholas S. Heaton
Keyword(s):  
Influenza A ◽  
Viral Disease ◽  
Viral Assembly ◽  
Influenza Viruses ◽  
Wild Type Virus ◽  
Wild Type ◽  
Influenza A Viruses ◽  
Viral Spread ◽  
Naturally Occurring ◽  
Viral Particles

AbstractInfluenza A viruses (IAVs) encode their genome as eight negative sense RNA segments. During viral assembly, the failure to package all eight segments, or packaging of a mutated segment, renders the resultant virion incompletely infectious. It is known that the accumulation of these defective particles can limit viral disease by interfering with the spread of fully infectious particles. In order to harness this phenomenon therapeutically, we defined which viral packaging signals were amenable to duplication and developed a viral genetic platform which allowed the production of replication competent IAVs that package up to two additional artificial genome segments for a total of 10 segments. These artificial genome segments are capable of acting as “decoy” segments that, when packaged by wild-type (WT) viruses, lead to the production of non-infectious viral particles. Despite 10-segmented viruses being able to replicate and spreadin vivo, these genomic modifications render the viruses avirulent. Excitingly, administration of 10-segmented viruses, both prophylactically and therapeutically, was able to rescue animals from normally lethally influenza virus infections. Thus, 10-segmented influenza viruses represent a potent anti-influenza biological therapy that targets the strain-independent process of viral assembly to slow the kinetics of productive viral spread and therefore limit viral disease.Author SummarySeasonal influenza infections are best prevented using vaccination. Vaccination, however, is not capable of completely preventing influenza infection, necessitating the use of anti-influenza therapeutics. To date, several different classes of anti-influenza therapeutics have been developed and used in order to combat these infections. Unfortunately, the incidence of influenza resistance to many of these therapeutics has begun to rise, necessitating the development of new strategies. One such strategy is to mimic the activity of naturally occurring viral particles that harbor defective genomes. These defective interfering particles have the ability to interfere with productive viral assembly, preventing the spread of influenza viruses across the respiratory tract. Furthermore, given the manner in which they target influenza segment packaging, a conserved feature of all influenza A viruses, resistance to this therapeutic strategy is unlikely. Here, we report the development of a genetic platform that allows the production of replication competent, 10-segmented influenza viruses. These viruses are capable of amplifying themselves in isolation, but co-infection with a wild-type virus leads to segment exchange and compromises the spread of both viruses. This interference, while mechanistically distinct from naturally occurring defective particles, was able to target the same viral process and rescue animals exposed to an otherwise lethal viral infection. This viral-based approach may represent a cost effective and scalable method to generate effective anti-influenza therapeutics when vaccines or anti-viral drugs become ineffective due to acquisition of viral resistance mutations.

scholarly journals Pathological Findings and Distribution of Pandemic Influenza A (H1N1) 2009 Virus in Lungs from Naturally Infected Fattening Pigs in Norway

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Mette Valheim ◽  
Hans Gamlem ◽  
Britt Gjerset ◽  
Anna Germundsson ◽  
Bjørn Lium
Keyword(s):  
Influenza A Virus ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Natural Infection ◽  
Experimental Studies ◽  
Influenza A Viruses ◽  
Lung Lesions ◽  
First Case ◽  
Influenza A H1n1 ◽  
Fattening Pigs

The Norwegian pig population was considered free from influenza A virus infections until the first case of porcine pandemic influenza A (H1N1) 2009 virus infection in October 2009. Human to pig transmission of virus was suspected. Unusual lung lesions were observed in fattening pigs, with red, lobular, multifocal to coalescing consolidation, most frequently in the cranial, middle, and accessory lobes. The main histopathological findings were epithelial degeneration and necrosis, lymphocyte infiltration in the epithelial lining and lamina propria of small bronchi and bronchioles, and peribronchial and peribronchiolar lymphocyte infiltrations. Infection with pandemic influenza A (H1N1) 2009 virus was confirmed by real-time RT-PCR and immunohistochemical detection of influenza A virus nucleoprotein in the lesions. This investigation shows that natural infection with the pandemic influenza A (H1N1) 2009 virus induces lung lesions similar to lesions described in experimental studies and natural infections with other swine-adapted subtypes of influenza A viruses.

Up to new tricks – A review of cross-species transmission of influenza A viruses

2007 ◽  
Vol 8 (1) ◽  
pp. 1-21 ◽  
Author(s):  
Gabriele A. Landolt ◽  
Christopher W. Olsen
Keyword(s):  
Influenza A Virus ◽  
Protective Immunity ◽  
Influenza A ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Virus Species ◽  
Influenza A Viruses ◽  
Ancient Times ◽  
Novel Virus ◽  
Do So

AbstractInfluenza is a highly contagious disease that has burdened both humans and animals since ancient times. In humans, the most dramatic consequences of influenza are associated with periodically occurring pandemics. Pandemics require the emergence of an antigenically novel virus to which the majority of the population lacks protective immunity. Historically, influenza A viruses from animals have contributed to the generation of human pandemic viruses and they may do so again in the future. It is, therefore, critical to understand the epidemiological and molecular mechanisms that allow influenza A viruses to cross species barriers. This review summarizes the current knowledge of influenza ecology, and the viral factors that are thought to determine influenza A virus species specificity.

scholarly journals Host Protective Immune Responses against Influenza A Virus Infection

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 504 ◽  
Author(s):  
Hi Eun Jung ◽  
Heung Kyu Lee
Keyword(s):  
Immune Responses ◽  
Influenza A ◽  
Current Knowledge ◽  
Influenza Viruses ◽  
Health Concern ◽  
Genetic Mutations ◽  
Public Health Concern ◽  
Influenza A Viruses ◽  
Influenza A Virus Infection ◽  
Influenza Outbreaks

Influenza viruses cause infectious respiratory disease characterized by fever, myalgia, and congestion, ranging in severity from mild to life-threating. Although enormous efforts have aimed to prevent and treat influenza infections, seasonal and pandemic influenza outbreaks remain a major public health concern. This is largely because influenza viruses rapidly undergo genetic mutations that restrict the long-lasting efficacy of vaccine-induced immune responses and therapeutic regimens. In this review, we discuss the virological features of influenza A viruses and provide an overview of current knowledge of the innate sensing of invading influenza viruses and the protective immune responses in the host.

scholarly journals Inferring the inter-host transmission of influenza A virus using patterns of intra-host genetic variation

2013 ◽  
Vol 280 (1750) ◽  
pp. 20122173 ◽  
Author(s):  
J. Conrad Stack ◽  
Pablo R. Murcia ◽  
Bryan T. Grenfell ◽  
James L. N. Wood ◽  
Edward C. Holmes
Keyword(s):  
Influenza A ◽  
Sequence Data ◽  
Control Strategies ◽  
Effective Control ◽  
Viral Gene ◽  
Influenza A Viruses ◽  
Susceptible Host ◽  
Wide Range ◽  
Natural Hosts ◽  
Transmission Studies

Influenza A viruses (IAVs) cause acute, highly transmissible infections in a wide range of animal species. Understanding how these viruses are transmitted within and between susceptible host populations is critical to the development of effective control strategies. While viral gene sequences have been used to make inferences about IAV transmission dynamics at the epidemiological scale, their utility in accurately determining patterns of inter-host transmission in the short-term—i.e. who infected whom—has not been strongly established. Herein, we use intra-host sequence data from the viral HA1 (hemagglutinin) gene domain from two transmission studies employing different IAV subtypes in their natural hosts—H3N8 in horses and H1N1 in pigs—to determine how well these data recapitulate the known pattern of inter-host transmission. Although no mutations were fixed over the course of either experimental transmission chain, we show that some minor, transient alleles can provide evidence of host-to-host transmission and, importantly, can be distinguished from those that cannot.

scholarly journals Comparison of Human-Like H1 (-Cluster) Influenza A Viruses in the Swine Host

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Janice R. Ciacci Zanella ◽  
Amy L. Vincent ◽  
Eraldo L. Zanella ◽  
Alessio Lorusso ◽  
Crystal L. Loving ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Lower Respiratory Tract ◽  
Influenza A ◽  
Control Strategies ◽  
Serum Antibody ◽  
Clinical Signs ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Antibody Titers

Influenza A viruses cause acute respiratory disease in swine. Viruses with H1 hemagglutinin genes from the human seasonal lineage (-cluster) have been isolated from North American swine since 2003. The objective of this work was to study the pathogenesis and transmission of -cluster H1 influenza viruses in swine, comparing three isolates from different phylogenetic subclusters, geographic locations, and years of isolation. Two isolates from the 2 subcluster, A/sw/MN/07002083/07 H1N1 (MN07) and A/sw/IL/00685/05 H1N1 (IL05), and A/sw/TX/01976/08 H1N2 (TX08) from the 1 sub-cluster were evaluated. All isolates caused disease and were transmitted to contact pigs. Respiratory disease was apparent in pigs infected with MN07 and IL05 viruses; however, clinical signs and lung lesions were reduced in severity as compared to TX08. On day 5 following infection MN07-infected pigs had lower virus titers than the TX08 pigs, suggesting that although this H1N1 was successfully transmitted, it may not replicate as efficiently in the upper or lower respiratory tract. MN07 and IL05 H1N1 induced higher serum antibody titers than TX08. Greater serological cross-reactivity was observed for viruses from the same HA phylogenetic sub-cluster; however, antigenic differences between the sub-clusters may have implications for disease control strategies for pigs.

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