scholarly journals A computational technique to estimate within-host productively infected cell lifetimes in emerging viral infections

Author(s):  
Soumya Banerjee

Emerging viruses cause a lot of fatalities as they jump to humans from other species. Here we develop a novel technique to computationally estimate an important parameter of within-host viral infection: the lifespan of infected cells. Our approach is general and can be applied to a large class of viruses and leverages experimental data from replicon studies. Current techniques have difficulties reliably estimating infected cell lifetimes due to issues of parameter identifiability and correlation of parameters. The infected cell lifetime is an important parameter that gives an estimate of the how fast virus levels will decline. Our method would also help determine if some infected cells are short-lived or have longer lifespans with the consequence that longer lived cells could be reservoirs of infection. This would give a mechanistic understanding of why particular cell types are reservoirs of infection. We apply our technique to West Nile virus (WNV), an emerging disease of public health relevance related to Zika virus. Our analysis suggests that the most abundant infectible cells are short-lived and could motivate therapy that targets these particular cells. Our approach is very general and can be combined with more traditional methods of using differential equation models to simulate viremia in hosts: the combination of these two techniques will likely yield results that may not be achievable using the models in isolation. This will be of great interest especially in modelling emerging diseases.

2017 ◽  
Author(s):  
Soumya Banerjee

Emerging viruses cause a lot of fatalities as they jump to humans from other species. Here we develop a novel technique to computationally estimate an important parameter of within-host viral infection: the lifespan of infected cells. Our approach is general and can be applied to a large class of viruses and leverages experimental data from replicon studies. Current techniques have difficulties reliably estimating infected cell lifetimes due to issues of parameter identifiability and correlation of parameters. The infected cell lifetime is an important parameter that gives an estimate of the how fast virus levels will decline. Our method would also help determine if some infected cells are short-lived or have longer lifespans with the consequence that longer lived cells could be reservoirs of infection. This would give a mechanistic understanding of why particular cell types are reservoirs of infection. We apply our technique to West Nile virus (WNV), an emerging disease of public health relevance related to Zika virus. Our analysis suggests that the most abundant infectible cells are short-lived and could motivate therapy that targets these particular cells. Our approach is very general and can be combined with more traditional methods of using differential equation models to simulate viremia in hosts: the combination of these two techniques will likely yield results that may not be achievable using the models in isolation. This will be of great interest especially in modelling emerging diseases.


2017 ◽  
Author(s):  
Soumya Banerjee

Emerging viruses cause a lot of fatalities as they jump to humans from other species. Here we develop a novel technique to computationally estimate an important parameter of within-host viral infection: the lifespan of infected cells. Our approach is general and can be applied to a large class of viruses and leverages experimental data from replicon studies. Current techniques have difficulties reliably estimating infected cell lifetimes due to issues of parameter identifiability and correlation of parameters. The infected cell lifetime is an important parameter that gives an estimate of the how fast virus levels will decline. Our method would also help determine if some infected cells are short-lived or have longer lifespans with the consequence that longer lived cells could be reservoirs of infection. This would give a mechanistic understanding of why particular cell types are reservoirs of infection. We apply our technique to West Nile virus (WNV), an emerging disease of public health relevance related to Zika virus. Our analysis suggests that the most abundant infectible cells are short-lived and could motivate therapy that targets these particular cells. Our approach is very general and can be combined with more traditional methods of using differential equation models to simulate viremia in hosts: the combination of these two techniques will likely yield results that may not be achievable using the models in isolation. This will be of great interest especially in modelling emerging diseases.


2019 ◽  
Author(s):  
soumya banerjee

What do fireflies and viruses have in common? Summary of paper titled A computational technique to estimate within-host productively infected cell lifetimes in emerging viral infections.


2007 ◽  
Vol 81 (10) ◽  
pp. 4973-4980 ◽  
Author(s):  
Michael S. Bennett ◽  
Hwee L. Ng ◽  
Mirabelle Dagarag ◽  
Ayub Ali ◽  
Otto O. Yang

ABSTRACT Cytotoxic T lymphocytes (CTLs) are crucial for immune control of viral infections. “Functional avidity,” defined by the sensitizing dose of exogenously added epitope yielding half-maximal CTL triggering against uninfected target cells (SD50), has been utilized extensively as a measure of antiviral efficiency. However, CTLs recognize infected cells via endogenously produced epitopes, and the relationship of SD50 to antiviral activity has never been directly revealed. We elucidate this relationship by comparing CTL killing of cells infected with panels of epitope-variant viruses to the corresponding SD50 for the variant epitopes. This reveals a steeply sigmoid relationship between avidity and infected cell killing, with avidity thresholds (defined as the SD50 required for CTL to achieve 50% efficiency of infected cell killing [KE50]), below which infected cell killing rapidly drops to none and above which killing efficiency rapidly plateaus. Three CTL clones recognizing the same viral epitope show the same KE50 despite differential recognition of individual epitope variants, while CTLs recognizing another epitope show a 10-fold-higher KE50, demonstrating epitope dependence of KE50. Finally, the ability of CTLs to suppress viral replication depends on the same threshold KE50. Thus, defining KE50 values is required to interpret the significance of functional avidity measurements and predict CTL efficacy against virus-infected cells in pathogenesis and vaccine studies.


2019 ◽  
Author(s):  
Jared L. Delahaye ◽  
Benjamin H. Gern ◽  
Sara B. Cohen ◽  
Courtney R. Plumlee ◽  
Shahin Shafiani ◽  
...  

AbstractGrowing evidence suggests the outcome of Mycobacterium tuberculosis (Mtb) infection is established rapidly after exposure, but how the current tuberculosis vaccine, BCG, impacts early immunity is poorly understood. Here we found that murine BCG immunization promotes a dramatic shift in infected cell types. While alveolar macrophages (AM) are the major infected cell for the first two weeks in unimmunized animals, BCG promotes the accelerated recruitment and infection of lung infiltrating phagocytes. Interestingly, this shift is dependent on CD4 T cells, yet does not require intrinsic recognition of antigen presented by infected AM. Mtb-specific T cells are first activated in lung regions devoid of infected cells, and these events precede vaccine-induced reduction of the bacterial burden, which occurs only after the co-localization of T cells and infected cells. Understanding how BCG alters early immune responses to Mtb provides new avenues to improve upon the immunity it confers.


Author(s):  
W. G. Banfield ◽  
G. Kasnic ◽  
J. H. Blackwell

An ultrastructural study of the intestinal epithelium of mice infected with the agent of epizootic diarrhea of infant mice (EDIM virus) was first performed by Adams and Kraft. We have extended their observations and have found developmental forms of the virus and associated structures not reported by them.Three-day-old NLM strain mice were infected with EDIM virus and killed 48 to 168 hours later. Specimens of bowel were fixed in glutaraldehyde, post fixed in osmium tetroxide and embedded in epon. Sections were stained with uranyl magnesium acetate followed by lead citrate and examined in an updated RCA EMU-3F electron microscope.The cells containing virus particles (infected) are at the tips of the villi and occur throughout the intestine from duodenum through colon. All developmental forms of the virus are present from 48 to 168 hours after infection. Figure 1 is of cells without virus particles and figure 2 is of an infected cell. The nucleus and cytoplasm of the infected cells appear clearer than the cells without virus particles.


2020 ◽  
Vol 15 (3) ◽  
pp. 219-232
Author(s):  
Ifrah Anwar ◽  
Usman A. Ashfaq ◽  
Zeeshan Shokat

The liver is a vital organ for life and the only internal organ that is capable of natural regeneration. Although the liver has high regeneration capacity, excessive hepatocyte death can lead to liver failure. Various factors can lead to liver damage including drug abuse, some natural products, alcohol, hepatitis, and autoimmunity. Some models for studying liver injury are APAP-based model, Fas ligand (FasL), D-galactosamine/endotoxin (Gal/ET), Concanavalin A, and carbon tetrachloride-based models. The regeneration of the liver can be carried out using umbilical cord blood stem cells which have various advantages over other stem cell types used in liver transplantation. UCB-derived stem cells lack tumorigenicity, have karyotype stability and high immunomodulatory, low risk of graft versus host disease (GVHD), low risk of transmitting somatic mutations or viral infections, and low immunogenicity. They are readily available and their collection is safe and painless. This review focuses on recent development and modern trends in the use of umbilical cord stem cells for the regeneration of liver fibrosis.


2020 ◽  
Vol 20 (4) ◽  
pp. 423-432 ◽  
Author(s):  
Imre Kovesdi ◽  
Tibor Bakacs

: Viral interference, originally, referred to a state of temporary immunity, is a state whereby infection with a virus limits replication or production of a second infecting virus. However, replication of a second virus could also be dominant over the first virus. In fact, dominance can alternate between the two viruses. Expression of type I interferon genes is many times upregulated in infected epithelial cells. Since the interferon system can control most, if not all, virus infections in the absence of adaptive immunity, it was proposed that viral induction of a nonspecific localized temporary state of immunity may provide a strategy to control viral infections. Clinical observations also support such a theory, which gave credence to the development of superinfection therapy (SIT). SIT is an innovative therapeutic approach where a non-pathogenic virus is used to infect patients harboring a pathogenic virus. : For the functional cure of persistent viral infections and for the development of broad- spectrum antivirals against emerging viruses a paradigm shift was recently proposed. Instead of the virus, the therapy should be directed at the host. Such a host-directed-therapy (HDT) strategy could be the activation of endogenous innate immune response via toll-like receptors (TLRs). Superinfection therapy is such a host-directed-therapy, which has been validated in patients infected with two completely different viruses, the hepatitis B (DNA), and hepatitis C (RNA) viruses. SIT exerts post-infection interference via the constant presence of an attenuated non-pathogenic avian double- stranded (ds) RNA viral vector which boosts the endogenous innate (IFN) response. SIT could, therefore, be developed into a biological platform for a new “one drug, multiple bugs” broad-spectrum antiviral treatment approach.


Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1468
Author(s):  
Yashika S. Kamte ◽  
Manisha N. Chandwani ◽  
Alexa C. Michaels ◽  
Lauren A. O’Donnell

Viruses that infect the central nervous system (CNS) are associated with developmental abnormalities as well as neuropsychiatric and degenerative conditions. Many of these viruses such as Zika virus (ZIKV), cytomegalovirus (CMV), and herpes simplex virus (HSV) demonstrate tropism for neural stem cells (NSCs). NSCs are the multipotent progenitor cells of the brain that have the ability to form neurons, astrocytes, and oligodendrocytes. Viral infections often alter the function of NSCs, with profound impacts on the growth and repair of the brain. There are a wide spectrum of effects on NSCs, which differ by the type of virus, the model system, the cell types studied, and the age of the host. Thus, it is a challenge to predict and define the consequences of interactions between viruses and NSCs. The purpose of this review is to dissect the mechanisms by which viruses can affect survival, proliferation, and differentiation of NSCs. This review also sheds light on the contribution of key antiviral cytokines in the impairment of NSC activity during a viral infection, revealing a complex interplay between NSCs, viruses, and the immune system.


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