Grand Challenge in Viral Disease Investigation: An Endless Endeavor (original) (raw)
2021, Frontiers in Virology
AI-generated Abstract
Viral diseases pose a persistent challenge to human health, evolving continuously and impacting various organisms. Despite historical advancements in virology, a profound understanding of viral pathogenesis remains elusive. Insights from animal models, particularly LCMV, have been instrumental in understanding viral-host dynamics, immune responses, and diseases related to viral immunosuppression. Modern techniques like deep sequencing unveil a complex virome within humans, revealing both pathogenic and nonpathogenic interactions. Addressing viral diseases through antiviral therapies is challenging due to the intricate nature of virus-infected cells, emphasizing the need for ongoing research and innovative treatment strategies.
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With the aim of characterizing the antiviral immune response to a non-cytocidal virus, we studied the outcome of lymphocytic choriomeningitis virus infection in a number of gene knockout mouse strains. Two virus strains di¡ering markedly in their capacity to spread and replicate inside the murine host were used. Our results reveal that very di¡erent outcomes may be observed depending on virus strain and immunocompetence of the host. Thus while CD4 + cells are not critical during the initial phase of virus control, infectious virus reappear in mice lacking CD4 + cells, B cells or CD40 ligand. Reappearance of virus is associated with impaired long-term CD8 + T-cell mediated immune surveillance, and the time to virus resurgence is inversely correlated to the replication rate of the virus. Our studies also reveal that interferon-g is a central cytokine, and depending on the rate of virus replication, mice lacking the ability to produce interferon-g may develop either a severe, mostly fatal, T-cell mediated wasting syndrome or a chronic infection characterized by long-term coexistence of antiviral cytotoxic T lymphocytes and infectious virus. Mathematical modelling indicates that these di¡erent outcomes may be explained in relatively simple mathematical terms. This suggests that modelling may be used as a means to predict critical host and virus parameters. Therefore, combining mathematical modelling with precise, quantitative, in vivo analyses looks to be a promising approach in addressing central quantitative issues in immunobiology.
This essay is designed to investigate the mystery of the virus: the smallest form of organic material that is able to replicate itself by following a parasitic approach that needs an external, living cell. As it is quite unable to metabolize nutrients, it is not considered to be alive. This essay will share some little known facts about viruses and help to dispel some dangerous myths that evolved about them and the vaccines used against them. Since 1892 when scientists started to investigate these objects, they have been confronted with the primary mystery: what are viruses? How do they survive on their endless quest from host to host? This essay will concentrate on the virulent viruses: those that cause a major threat to humanity; we will focus on the Big Three: smallpox, polio and influenza. The influenza story becomes central because it illustrates the false assumptions that have been made in the past with earlier false alarms, such as the Swine Flu panic of 1976 and the even larger false assumptions about the 'Great Spanish Flu Pandemic' of 1918-1920, where most deaths were due to deadly bacteria. The present covid panic seems to be a reflection of the 1976 Swine Flu panic. Several other viruses are examined (like Hepatitis B and the Herpes family: Herpes Simplex and Epstein-Barr) as they illustrate the successful vaccines used to defeat them; interestingly, this has NOT been used here in the current Covid Panic. This study of viruses has increased my respect for the variety of nature, no matter what its scale but a better understanding of how they function will help us react to their ongoing threats. Knowing their structure, is only the first step in understanding what is going on: processes are more significant than structure (relationships are key to knowledge; not just identifying-and naming-objects). Although written for an educated audience (but not virologists) there is much here of interest to non-scientists to show HOW real virology is done (slowly: one discovery at a time). I hope this great story will appeal to many.
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