scholarly journals Bile Facilitates Human Norovirus Interactions with Diverse Histoblood Group Antigens, Compensating for Capsid Microvariation Observed in 2016–2017 GII.2 Strains

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 989
Author(s):  
Michael L. Mallory ◽  
Lisa C. Lindesmith ◽  
Paul D. Brewer-Jensen ◽  
Rachel L. Graham ◽  
Ralph S. Baric
Keyword(s):  
Mucosal Immunity ◽  
Bile Salts ◽  
Rapid Evolution ◽  
Blood Group Antigen ◽  
Host Factors ◽  
Viral Capsid ◽  
Human Populations ◽  
Human Norovirus ◽  
Sudden Rise ◽  
Limited Sequence

Human norovirus (HuNoV) is the leading cause of global infectious acute gastroenteritis, causing ~20% of reported diarrheal episodes. Typically, GII.4 strains cause 50–70% of yearly outbreaks, and pandemic waves of disease approximately every 2–7 years due to rapid evolution. Importantly, GII.4 dominance is occasionally challenged by the sudden emergence of other GII strains, most recently by GII.2 strains which peaked in 2016–2017, dramatically increasing from 1% to 20% of total HuNoV outbreaks. To determine if viral capsid evolution may account for the sudden rise in GII.2 outbreaks, Virus Like Particles (VLPs) of two 2016–2017 GII.2 strains were compared by antigenic and histo blood group antigen (HBGA) binding profiles to the prototypic 1976 GII.2 Snow Mountain Virus (SMV) strain. Despite >50 years of GII.2 strain persistence in human populations, limited sequence diversity and antigenic differences were identified between strains. However, capsid microvariation did affect HBGA binding patterns, with contemporary strains demonstrating decreased avidity for type A saliva. Furthermore, bile salts increased GII.2 VLP avidity for HBGAs, but did not alter antigenicity. These data indicate that large changes in antigenicity or receptor binding are unlikely to explain GII.2 emergence, in contrast to the pandemic GII.4 strains, and indicate that host factors such as waning or remodeling of serum or mucosal immunity likely contributed to the surge in GII.2 prevalence.

Characterization of a Histo-Blood Group Antigen-like Substance in Romaine Lettuce That Contributes to Human Norovirus Attachment

2019 ◽  
Vol 68 (5) ◽  
pp. 1207-1212 ◽  
Author(s):  
Zilei Zhang ◽  
Danlei Liu ◽  
Qingping Wu ◽  
Yu Lu ◽  
Peng Tian ◽  
...  
Keyword(s):  
Blood Group ◽  
Blood Group Antigen ◽  
Romaine Lettuce ◽  
Human Norovirus

scholarly journals Natural deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape

2020 ◽  
Author(s):  
Kevin R. McCarthy ◽  
Linda J. Rennick ◽  
Sham Nambulli ◽  
Lindsey R. Robinson-McCarthy ◽  
William G. Bain ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Rna Viruses ◽  
Rapid Evolution ◽  
Neutralizing Antibody ◽  
Antigenic Drift ◽  
Human Populations ◽  
Spike Glycoprotein ◽  
Evolutionary Pattern ◽  
Antigenic Sites ◽  
Global Pandemic

AbstractZoonotic pandemics follow the spillover of animal viruses into highly susceptible human populations. Often, pandemics wane, becoming endemic pathogens. Sustained circulation requires evasion of protective immunity elicited by previous infections. The emergence of SARS-CoV-2 has initiated a global pandemic. Since coronaviruses have a lower substitution rate than other RNA viruses this gave hope that spike glycoprotein is an antigenically stable vaccine target. However, we describe an evolutionary pattern of recurrent deletions at four antigenic sites in the spike glycoprotein. Deletions abolish binding of a reported neutralizing antibody. Circulating SARS-CoV-2 variants are continually exploring genetic and antigenic space via deletion in individual patients and at global scales. In viruses where substitutions are relatively infrequent, deletions represent a mechanism to drive rapid evolution, potentially promoting antigenic drift.

scholarly journals Genetic Susceptibility to Human Norovirus Infection: An Update

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 226 ◽  
Author(s):  
Johan Nordgren ◽  
Lennart Svensson
Keyword(s):  
Genetic Susceptibility ◽  
Blood Group ◽  
Phenotypic Diversity ◽  
In Vivo Studies ◽  
Human Populations ◽  
Blood Group Antigens ◽  
Human Norovirus ◽  
The Impact ◽  
High Infectivity

Noroviruses are the most common etiological agent of acute gastroenteritis worldwide. Despite their high infectivity, a subpopulation of individuals is resistant to infection and disease. This susceptibility is norovirus genotype-dependent and is largely mediated by the presence or absence of human histo-blood group antigens (HBGAs) on gut epithelial surfaces. The synthesis of these HBGAs is mediated by fucosyl- and glycosyltransferases under the genetic control of the FUT2 (secretor), FUT3 (Lewis) and ABO(H) genes. The so-called non-secretors, having an inactivated FUT2 enzyme, do not express blood group antigens and are resistant to several norovirus genotypes, including the predominant GII.4. Significant genotypic and phenotypic diversity of HBGA expression exists between different human populations. Here, we review previous in vivo studies on genetic susceptibility to norovirus infection. These are discussed in relation to population susceptibility, vaccines, norovirus epidemiology and the impact on public health.

scholarly journals The kinetoplastid-infecting Bodo saltans virus (BsV), a window into the most abundant giant viruses in the sea

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Christoph M Deeg ◽  
Cheryl-Emiliane T Chow ◽  
Curtis A Suttle
Keyword(s):  
Aquatic Ecosystems ◽  
Homing Endonuclease ◽  
Rapid Evolution ◽  
Host Factors ◽  
Metagenomic Data ◽  
Replication Machinery ◽  
Genomic Plasticity ◽  
Giant Viruses ◽  
Translational Apparatus ◽  
Self Splicing

Giant viruses are ecologically important players in aquatic ecosystems that have challenged concepts of what constitutes a virus. Herein, we present the giant Bodo saltans virus (BsV), the first characterized representative of the most abundant group of giant viruses in ocean metagenomes, and the first isolate of a klosneuvirus, a subgroup of the Mimiviridae proposed from metagenomic data. BsV infects an ecologically important microzooplankton, the kinetoplastid Bodo saltans. Its 1.39 Mb genome encodes 1227 predicted ORFs, including a complex replication machinery. Yet, much of its translational apparatus has been lost, including all tRNAs. Essential genes are invaded by homing endonuclease-encoding self-splicing introns that may defend against competing viruses. Putative anti-host factors show extensive gene duplication via a genomic accordion indicating an ongoing evolutionary arms race and highlighting the rapid evolution and genomic plasticity that has led to genome gigantism and the enigma that is giant viruses.

scholarly journals The kinetoplastid-infecting Bodo saltans virus (BsV), a window into the most abundant giant viruses in the sea

2017 ◽  
Author(s):  
Christoph M. Deeg ◽  
Cheryl-Emiliane T. Chow ◽  
Curtis A. Suttle
Keyword(s):  
Aquatic Ecosystems ◽  
Homing Endonuclease ◽  
Rapid Evolution ◽  
Host Factors ◽  
Metagenomic Data ◽  
Genomic Plasticity ◽  
Translational Machinery ◽  
Independent Replication ◽  
Giant Viruses ◽  
Self Splicing

AbstractGiant viruses are ecologically important players in aquatic ecosystems that have challenged concepts of what constitutes a virus. Herein, we present the giant Bodo saltans virus (BsV), the first characterized representative of the most abundant giant viruses in the oceans, and the first klosneuvirus isolate, a subgroup of theMimiviridaeproposed from metagenomic data. BsV infects an ecologically important microzooplankton, the kinetoplastidBodo saltans. Its 1.39 Mb genome is the largest described for theMimiviridaeand encodes 1227 predicted ORFs, including pathways for host-independent replication. Yet, much of its translational machinery has been lost, including all tRNAs. Essential genes are invaded by homing endonuclease-encoding self-splicing introns that may defend against competing viruses. Putative anti-host factors show extensive gene duplication via a genomic accordion indicating an ongoing evolutionary arms race and highlighting the rapid evolution and genomic plasticity that has led to genome gigantism and the enigma that is giant viruses.

scholarly journals Macrophage-specific responses to human- and animal-adapted tubercle bacilli reveal pathogen and host factors driving multinucleated cell formation

2020 ◽  
Author(s):  
Christophe J. Queval ◽  
Antony Fearns ◽  
Laure Botella ◽  
Alicia Smyth ◽  
Laura Schnettger ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Cell Formation ◽  
Host Factors ◽  
Human Populations ◽  
Host Tropism ◽  
Multinucleated Cells ◽  
Main Host ◽  
Species Specific ◽  
Cellular Compartments

AbstractThe Mycobacterium tuberculosis complex (MTBC) is a group of related pathogens that cause tuberculosis (TB) in mammals. MTBC species are distinguished by their ability to sustain in distinct host populations. While Mycobacterium bovis (Mbv) sustains transmission cycles in cattle and wild animals and causes zoonotic TB, M. tuberculosis (Mtb) affects human populations and seldom causes disease in cattle. However, the host and pathogen determinants driving host tropism between MTBC species are still unknown. Macrophages are the main host cell that encounters mycobacteria upon initial infection and we hypothesised that early interactions between the macrophage and mycobacteria influence species-specific disease outcome. To identify factors that contribute to host tropism, we analysed both blood-derived primary human and bovine macrophages (hMϕ or bMϕ, respectively) infected with Mbv and Mtb. We show that Mbv and Mtb reside in different cellular compartments and differentially replicate in hMϕ whereas both Mbv and Mtb efficiently replicate in bMϕ. Specifically, we show that out of the four infection combinations, only the infection of bMϕ with Mbv promoted the formation of multinucleated cells (MNCs), a hallmark of tuberculous granulomas. Mechanistically, we demonstrate that both MPB70 from Mbv and extracellular vesicles released by Mbv-infected bMϕ promote macrophage multi-nucleation. Importantly, we extend our in vitro studies to show that granulomas from Mbv-infected but not Mtb-infected cattle contained higher numbers of MNCs. Our findings implicate MNC formation in the contrasting pathology between Mtb and Mbv for the bovine host, and identify MPB70 from Mbv and extracellular vesicles from bMϕ as mediators of this process.

scholarly journals Roles of Capsid-Interacting Host Factors in Multimodal Inhibition of HIV-1 by PF74

2016 ◽  
Vol 90 (12) ◽  
pp. 5808-5823 ◽  
Author(s):  
Akatsuki Saito ◽  
Damien Ferhadian ◽  
Gregory A. Sowd ◽  
Erik Serrao ◽  
Jiong Shi ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Dose Response ◽  
Response Curve ◽  
Cyclophilin A ◽  
Dose Response Curve ◽  
Host Factors ◽  
Viral Capsid ◽  
Antiviral Compound ◽  
Drug Concentrations ◽  
Hiv 1

ABSTRACTThe viral capsid of HIV-1 interacts with a number of host factors to orchestrate uncoating and regulate downstream events, such as reverse transcription, nuclear entry, and integration site targeting. PF-3450074 (PF74), an HIV-1 capsid-targeting low-molecular-weight antiviral compound, directly binds to the capsid (CA) protein at a site also utilized by host cell proteins CPSF6 and NUP153. Here, we found that the dose-response curve of PF74 is triphasic, consisting of a plateau and two inhibitory phases of different slope values, consistent with a bimodal mechanism of drug action. High PF74 concentrations yielded a steep curve with the highest slope value among different classes of known antiretrovirals, suggesting a dose-dependent, cooperative mechanism of action. CA interactions with both CPSF6 and cyclophilin A (CypA) were essential for the unique dose-response curve. A shift of the steep curve at lower drug concentrations upon blocking the CA-CypA interaction suggests a protective role for CypA against high concentrations of PF74. These findings, highlighting the unique characteristics of PF74, provide a model in which its multimodal mechanism of action of both noncooperative and cooperative inhibition by PF74 is regulated by interactions of cellular proteins with incoming viral capsids.IMPORTANCEPF74, a novel capsid-targeting antiviral against HIV-1, shares its binding site in the viral capsid protein (CA) with the host factors CPSF6 and NUP153. This work reveals that the dose-response curve of PF74 consists of two distinct inhibitory phases that are differentially regulated by CA-interacting host proteins. PF74's potency depended on these CA-binding factors at low doses. In contrast, the antiviral activity of high PF74 concentrations was attenuated by cyclophilin A. These observations provide novel insights into both the mechanism of action of PF74 and the roles of host factors during the early steps of HIV-1 infection.

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