scholarly journals Running With Scissors: Evolutionary Conflicts Between Viral Proteases and the Host Immune System

2021 ◽  
Vol 12 ◽  
Author(s):  
Brian V. Tsu ◽  
Elizabeth J. Fay ◽  
Katelyn T. Nguyen ◽  
Miles R. Corley ◽  
Bindhu Hosuru ◽  
...  
Keyword(s):  
Immune System ◽  
Gene Evolution ◽  
Evolutionary Constraint ◽  
Host Immune System ◽  
Viral Protease ◽  
Host Interactions ◽  
Cellular Processes ◽  
Protease Cleavage ◽  
Viral Proteases ◽  
Protease Cleavage Sites

Many pathogens encode proteases that serve to antagonize the host immune system. In particular, viruses with a positive-sense single-stranded RNA genome [(+)ssRNA], including picornaviruses, flaviviruses, and coronaviruses, encode proteases that are not only required for processing viral polyproteins into functional units but also manipulate crucial host cellular processes through their proteolytic activity. Because these proteases must cleave numerous polyprotein sites as well as diverse host targets, evolution of these viral proteases is expected to be highly constrained. However, despite this strong evolutionary constraint, mounting evidence suggests that viral proteases such as picornavirus 3C, flavivirus NS3, and coronavirus 3CL, are engaged in molecular ‘arms races’ with their targeted host factors, resulting in host- and virus-specific determinants of protease cleavage. In cases where protease-mediated cleavage results in host immune inactivation, recurrent host gene evolution can result in avoidance of cleavage by viral proteases. In other cases, such as recently described examples in NLRP1 and CARD8, hosts have evolved ‘tripwire’ sequences that mimic protease cleavage sites and activate an immune response upon cleavage. In both cases, host evolution may be responsible for driving viral protease evolution, helping explain why viral proteases and polyprotein sites are divergent among related viruses despite such strong evolutionary constraint. Importantly, these evolutionary conflicts result in diverse protease-host interactions even within closely related host and viral species, thereby contributing to host range, zoonotic potential, and pathogenicity of viral infection. Such examples highlight the importance of examining viral protease-host interactions through an evolutionary lens.

scholarly journals Globally defining the effects of mutations in a picornavirus capsid

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Florian Mattenberger ◽  
Victor Latorre ◽  
Omer Tirosh ◽  
Adi Stern ◽  
Ron Geller
Keyword(s):  
Viral Fitness ◽  
Sequence Specificity ◽  
Protein Assemblies ◽  
Multifunctional Protein ◽  
Host Interactions ◽  
Fitness Effects ◽  
Protease Cleavage ◽  
Viral Proteases ◽  
Novel Host ◽  
Protease Cleavage Sites

The capsids of non-enveloped viruses are highly multimeric and multifunctional protein assemblies that play key roles in viral biology and pathogenesis. Despite their importance, a comprehensive understanding of how mutations affect viral fitness across different structural and functional attributes of the capsid is lacking. To address this limitation, we globally define the effects of mutations across the capsid of a human picornavirus. Using this resource, we identify structural and sequence determinants that accurately predict mutational fitness effects, refine evolutionary analyses, and define the sequence specificity of key capsid-encoded motifs. Furthermore, capitalizing on the derived sequence requirements for capsid-encoded protease cleavage sites, we implement a bioinformatic approach for identifying novel host proteins targeted by viral proteases. Our findings represent the most comprehensive investigation of mutational fitness effects in a picornavirus capsid to date and illuminate important aspects of viral biology, evolution, and host interactions.

scholarly journals The Bacterium Frischella perrara Causes Scab Formation in the Gut of its Honeybee Host

mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Philipp Engel ◽  
Kelsey D. Bartlett ◽  
Nancy A. Moran
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Gut Microbiota ◽  
Bacterial Colonization ◽  
Bacterial Species ◽  
Host Immune System ◽  
Natural Ecosystems ◽  
Epithelial Surface ◽  
Host Interactions ◽  
Key Species

ABSTRACT Honeybees harbor well-defined bacterial communities in their guts. The major members of these communities appear to benefit the host, but little is known about how they interact with the host and specifically how they interface with the host immune system. In the pylorus, a short region between the midgut and hindgut, honeybees frequently exhibit scab-like structures on the epithelial gut surface. These structures are reminiscent of a melanization response of the insect immune system. Despite the wide distribution of this phenotype in honeybee populations, its cause has remained elusive. Here, we show that the presence of a common member of the bee gut microbiota, the gammaproteobacterium Frischella perrara, correlates with the appearance of the scab phenotype. Bacterial colonization precedes scab formation, and F. perrara specifically localizes to the melanized regions of the host epithelium. Under controlled laboratory conditions, we demonstrate that exposure of microbiota-free bees to F. perrara but not to other bacteria results in scab formation. This shows that F. perrara can become established in a spatially restricted niche in the gut and triggers a morphological change of the epithelial surface, potentially due to a host immune response. As an intermittent colonizer, this bacterium holds promise for addressing questions of community invasion in a simple yet relevant model system. Moreover, our results show that gut symbionts of bees engage in differential host interactions that are likely to affect gut homeostasis. Future studies should focus on how these different gut bacteria impact honeybee health. IMPORTANCE As pollinators, honeybees are key species for agricultural and natural ecosystems. Their guts harbor simple communities composed of characteristic bacterial species. Because of these features, bees are ideal systems for studying fundamental aspects of gut microbiota-host interactions. However, little is known about how these bacteria interact with their host. Here, we show that a common member of the bee gut microbiota causes the formation of a scab-like structure on the gut epithelium of its host. This phenotype was first described in 1946, but since then it has not been much further characterized, despite being found in bee populations worldwide. The scab phenotype is reminiscent of melanization, a conserved innate immune response of insects. Our results show that high abundance of one member of the bee gut microbiota triggers this specific phenotype, suggesting that the gut microbiota composition can affect the immune status of this key pollinator species.

scholarly journals Glycans in Virus-Host Interactions: A Structural Perspective

2021 ◽  
Vol 8 ◽  
Author(s):  
Nathaniel L. Miller ◽  
Thomas Clark ◽  
Rahul Raman ◽  
Ram Sasisekharan
Keyword(s):  
Immune System ◽  
Host Cells ◽  
Host Immune System ◽  
Host Interactions ◽  
Viral Glycoproteins ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Anti Hiv ◽  
Structural Perspective

Many interactions between microbes and their hosts are driven or influenced by glycans, whose heterogeneous and difficult to characterize structures have led to an underappreciation of their role in these interactions compared to protein-based interactions. Glycans decorate microbe glycoproteins to enhance attachment and fusion to host cells, provide stability, and evade the host immune system. Yet, the host immune system may also target these glycans as glycoepitopes. In this review, we provide a structural perspective on the role of glycans in host-microbe interactions, focusing primarily on viral glycoproteins and their interactions with host adaptive immunity. In particular, we discuss a class of topological glycoepitopes and their interactions with topological mAbs, using the anti-HIV mAb 2G12 as the archetypical example. We further offer our view that structure-based glycan targeting strategies are ready for application to viruses beyond HIV, and present our perspective on future development in this area.

scholarly journals A novel vaccine targeting the viral protease cleavage sites protects Mauritian cynomolgus macaques against vaginal SIVmac251 infection

2019 ◽  
Author(s):  
Hongzhao Li ◽  
Robert W. Omange ◽  
Binhua Liang ◽  
Nikki Toledo ◽  
Yan Hai ◽  
...  
Keyword(s):  
T Cell ◽  
Vaccine Efficacy ◽  
T Cell Responses ◽  
Hiv Vaccine ◽  
Cleavage Sites ◽  
Viral Protease ◽  
Cell Responses ◽  
Protease Cleavage ◽  
Cynomolgus Macaques ◽  
Protease Cleavage Sites

AbstractAfter over three decades of research, an effective anti-HIV vaccine remains elusive. Unconventional and novel vaccine strategies are needed. Here, we report that a vaccine focusing the immune response on the sequences surrounding the 12 viral protease cleavage sites (PCSs) provides greater than 80% protection of Mauritian cynomolgus macaques (MCMs) against repeated intravaginal SIVmac251 challenges. The PCS-specific T cell responses are correlated with vaccine efficacy. The PCS vaccine does not induce immune activation and inflammation known to be associated with increased susceptibility to HIV infection. Machine learning analyses revealed that the immune environment generated by the PCS vaccine predicts vaccine efficacy. Our study demonstrates for the first time that a novel vaccine which targets viral maturation, but lacks full Env and Gag proteins as immunogens, can prevent intravaginal infection in a highly stringent NHP/SIV challenge model. Targeting HIV maturation thus offers a novel approach to developing an effective HIV vaccine.One Sentence SummaryThe anti-PCS T cell responses and the immune environment induced by the novel PCS vaccine are key correlates of vaccine efficacy

scholarly journals Antimicrobial peptides and cell processes tracking endosymbiont dynamics

2016 ◽  
Vol 371 (1695) ◽  
pp. 20150298 ◽  
Author(s):  
Florent Masson ◽  
Anna Zaidman-Rémy ◽  
Abdelaziz Heddi
Keyword(s):  
Immune System ◽  
Antimicrobial Peptides ◽  
Evolutionary Ecology ◽  
Host Cells ◽  
Host Immune System ◽  
Free Living ◽  
Cellular Processes ◽  
Cell Processes ◽  
And Control

Many insects sustain long-term relationships with intracellular symbiotic bacteria that provide them with essential nutrients. Such endosymbiotic relationships likely emerged from ancestral infections of the host by free-living bacteria, the genomes of which experience drastic gene losses and rearrangements during the host–symbiont coevolution. While it is well documented that endosymbiont genome shrinkage results in the loss of bacterial virulence genes, whether and how the host immune system evolves towards the tolerance and control of bacterial partners remains elusive. Remarkably, many insects rely on a ‘compartmentalization strategy’ that consists in secluding endosymbionts within specialized host cells, the bacteriocytes, thus preventing direct symbiont contact with the host systemic immune system. In this review, we compile recent advances in the understanding of the bacteriocyte immune and cellular regulators involved in endosymbiont maintenance and control. We focus on the cereal weevils Sitophilus spp., in which bacteriocytes form bacteriome organs that strikingly evolve in structure and number according to insect development and physiological needs. We discuss how weevils track endosymbiont dynamics through at least two mechanisms: (i) a bacteriome local antimicrobial peptide synthesis that regulates endosymbiont cell cytokinesis and helps to maintain a homeostatic state within bacteriocytes and (ii) some cellular processes such as apoptosis and autophagy which adjust endosymbiont load to the host developmental requirements, hence ensuring a fine-tuned integration of symbiosis costs and benefits. This article is part of the themed issue ‘Evolutionary ecology of arthropod antimicrobial peptides’.

Role of Vasavaleha in the management of Covid19

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 259-261
Author(s):  
Aamir Khan ◽  
Rajni K. Gurmule
Keyword(s):  
Immune System ◽  
Human Body ◽  
Respiratory Diseases ◽  
Spreading Rate ◽  
Host Immune System ◽  
Shortness Of Breath ◽  
Antitussive Effect ◽  
Corona Viruses ◽  
Very High

Vasavaleha is one of the best medicine given for respiratory diseases. Corona viruses typically affect the respiratory system, causing symptoms such as coughing, fever and shortness of breath. It also affects host immune system of human body. Spreading rate of this disease is very high. Whole world is seeking for the treatment which can uproots this diseases. There in no vaccine available till date against this pandemic disease. Ayurveda mainly focuses on prevention of diseases alongwith its total cure. Rajyakshma Vyadhi is MadhyamMarga Roga as per Ayurveda. It shows many symptoms such as Kasa, Shwasa etc. By overall view of Covid 19, shows its resemblance with Rajyakshma Vyadhi described in Ayurveda. Vasavaleha is a Kalpa which is described in Rogadhikara of Rajyakshma. It shows Kasahara, Shwashara properties. It consists of Vasa, Pipalli, Madhu and Goghrita. These components shows actions like bronchodilation, antitussive effect and many more other actions. Pipalli shows important Rasayana effect. So in present review, we have tried to focus on role of Vasavaleha in the management of Covid 19. This can be used as preventive as well as adjuvant medication in treating Covid 19. There is need of further clinical research to rule of exact action of Vasavaleha against Covid 19.

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