Drareg
Member
- Joined
- Feb 18, 2016
- Messages
- 4,772
Mentioned recently in a KMUD radio interview, it’s interesting this guy with his vast experience in coronaviruses has little media presence, some articles were done on him but you’d think he should be the go to "expert" for the "expert selectors", conveniently left out probably because his research is basically modifying mice to carry coronavirus.
I find the line about the presence of coronaviruses in populations with chronic underlying diseases interesting, it’s natural state of infectiousness makes it perfect for a modification targeting a specific cohort of the population, subtle eugenics. It’s clearly an ambition of the likes of Bill Epstein Gates.
The one positive from this is the psychopaths clearly perceive and project through the lens/paradigm of "receptors" , is it reasonable to guess that a receptor isn’t created but a receptive capacity is via cell excitability? He mentions in the study below that his mouse modifications contain innate immune response defects.
I understand a peptide can be created to carry the virus into the cell but is it possible that animals with a higher more coherent metabolic state just overcome them via the immune response, is it so efficient at responding to the virus that our method of testing doesn’t pick it up?
According to this study coronaviruses are a perfect for targeting specific organs for directed gene expression, the coronavirus genome is unique, it can have seven kilobases of foreign genetic material uploaded to its genome and they are stable !
Thankfully this lot are still tainted by genetic determinism and receptors theories, in their world of delusion they believe a virus can be created to specifically effect the heart via the genome incurring a permanent change, they pre-create the pill to treat it, they don’t want folks to die because where is the profit in that however a chronic change for life is, its basically the window salesman who breaks windows at night.
One such study is the following-
https://dacemirror.sci-hub.se/journ...2656e237e5a595186/baric2005.pdf?download=true
Coronavirus infections historically were associated with mild upper respiratory tract diseases in in- fants, children, and adults. Human coronavirus (HCoV)-OC43 and HCoV-229E were associated with 15–30% of common colds in winter and occasionally linked with lower respiratory tract disease in populations with chronic under- lying diseases. HCoV research was com- plicated by the lack of a reverse genetic system or animal model. These viruses propagated poorly, and the number of reagents was limited. However, coronavi- ruses are capable of rapid host switching and evolution in changing ecologies (1), suggesting that their diversity and role in human disease were underappreciated. The 21st century heralded the arrival of the more pathogenic coronaviruses, like severe acute respiratory syndrome (SARS)-CoV. Then, HCoV-NL63 was identified as an important cause of severe lower respiratory tract infections in chil- dren and adults, including a tentative link- age with Kawasaki disease (2), and HCoV-HKU1 was identified in adults with pneumonia (3–5), renewing interest in the replication mechanisms and patho- genesis of HCoV-OC43 and HCoV-229E. In this issue of PNAS, Lassnig et al. (6) describe a transgenic mouse model to study HCoV-229E replication and patho- genesis, laying the groundwork for devel- oping transgenic mouse models for other HCOVS.
Animal Models of Human Disease
The receptor for HCoV-229E, hAPN, also termed CD13, is a 150-kDa membrane- bound exopeptidase, which is constitutively expressed and forms dimers on the surface of a wide variety of cells (10). APN functions in digestion, angiogenesis, and synaptic activity and cleaves peptides bound to MHC molecules of antigen- presenting cells. Transfection of nonper- missive cells with hAPN is sufficient to confer susceptibility to HCoV-229E infec- tion (10). For the group 1 coronaviruses, early attempts at developing transgenic mice expressing the hAPN receptor failed to produce a susceptible model, suggesting that other cofactors might be essential for in vivo replication (14). This outcome is not unique to HCoV-229E; similar findings were reported in transgenic mice expressing the poliovirus and measles virus receptors (15). Although the fundamental basis for this dichotomy remains undetermined, modifications that enhanced virus growth in these models included the generation of doubletransgenic mice that also contained defects in innate immune responses, virus strain variation, or changes in the route of inoculation.
Future Directions
Lassnig et al.’s article (6) provides a para- digm for the generation of transgenic animals that are susceptible to HCoVs. SARS-CoV replicates efficiently in BALBc mice without significant clinical disease or pathology, limiting the useful- ness of this model for viral pathogenesis studies and the identification of virulence determinants (20). The development of human angiotensin-converting enzyme 2 transgenic animals may well serve as a more robust model for SARS-CoV. Im- portantly, hAPN humanized mice allow studies into HCoV-229E pathogenesis, tropism, replication, and spread in an immunocompromised host. hAPN is highly polymorphic in human populations, and the availability of this animal model al- lows investigation into whether allelic variation in the receptor inf luences HCoV-229E replication and pathogenesis in vivo, as has been so elegantly described for other RNA viruses like noroviruses (21, 22). The molecular basis for HCoV- 229E adaptation represents another rich avenue of investigation. Although the S glycoprotein may be critical, other genetic changes could equally contribute to in vivo replication, adaptation, and pathogenesis. Because virus entry and spread are often- times restricted by innate host defense mechanisms, it is likely that one or more mutations may evolve that restrict activa- tion of antiviral host genes in Stat/
mice. The molecular clone for HCoV- 229E provides the necessary tool for the identification and functional analysis of genetic elements responsible for in vivo adaptation and pathogenesis.
Murine models for HCoV-229E and SARS-CoV infection provide a means to study viral vector tropism and the efficacy and biosafety of HCoV-based vaccine vectors. The coronaviruses’ unique genome organization and replication strategy allow simultaneous regulated expression of multiple foreign genes from transcription regulatory sequences encoded at the 3 end of the genome. Coronavirus vectors can be targeted to different species, tissues, and mucosal compartments allowing for directed gene expression. It is likely that several kilobases of foreign genetic material can be stably incorporated and expressed in coronavirus genomes. HCoV vectors can be designed to safely target payloads to specific tissues or organs (13). The achievement by Lassnig et al. (6) will encourage further studies into human coronavirus replication and pathogenesis in vivo while simultaneously propelling the development of second-generation animal models for applying coronavirus-based vaccines and therapeutics in the treatment of human diseases.
I find the line about the presence of coronaviruses in populations with chronic underlying diseases interesting, it’s natural state of infectiousness makes it perfect for a modification targeting a specific cohort of the population, subtle eugenics. It’s clearly an ambition of the likes of Bill Epstein Gates.
The one positive from this is the psychopaths clearly perceive and project through the lens/paradigm of "receptors" , is it reasonable to guess that a receptor isn’t created but a receptive capacity is via cell excitability? He mentions in the study below that his mouse modifications contain innate immune response defects.
I understand a peptide can be created to carry the virus into the cell but is it possible that animals with a higher more coherent metabolic state just overcome them via the immune response, is it so efficient at responding to the virus that our method of testing doesn’t pick it up?
According to this study coronaviruses are a perfect for targeting specific organs for directed gene expression, the coronavirus genome is unique, it can have seven kilobases of foreign genetic material uploaded to its genome and they are stable !
Thankfully this lot are still tainted by genetic determinism and receptors theories, in their world of delusion they believe a virus can be created to specifically effect the heart via the genome incurring a permanent change, they pre-create the pill to treat it, they don’t want folks to die because where is the profit in that however a chronic change for life is, its basically the window salesman who breaks windows at night.
One such study is the following-
https://dacemirror.sci-hub.se/journ...2656e237e5a595186/baric2005.pdf?download=true
Coronavirus infections historically were associated with mild upper respiratory tract diseases in in- fants, children, and adults. Human coronavirus (HCoV)-OC43 and HCoV-229E were associated with 15–30% of common colds in winter and occasionally linked with lower respiratory tract disease in populations with chronic under- lying diseases. HCoV research was com- plicated by the lack of a reverse genetic system or animal model. These viruses propagated poorly, and the number of reagents was limited. However, coronavi- ruses are capable of rapid host switching and evolution in changing ecologies (1), suggesting that their diversity and role in human disease were underappreciated. The 21st century heralded the arrival of the more pathogenic coronaviruses, like severe acute respiratory syndrome (SARS)-CoV. Then, HCoV-NL63 was identified as an important cause of severe lower respiratory tract infections in chil- dren and adults, including a tentative link- age with Kawasaki disease (2), and HCoV-HKU1 was identified in adults with pneumonia (3–5), renewing interest in the replication mechanisms and patho- genesis of HCoV-OC43 and HCoV-229E. In this issue of PNAS, Lassnig et al. (6) describe a transgenic mouse model to study HCoV-229E replication and patho- genesis, laying the groundwork for devel- oping transgenic mouse models for other HCOVS.
Animal Models of Human Disease
The receptor for HCoV-229E, hAPN, also termed CD13, is a 150-kDa membrane- bound exopeptidase, which is constitutively expressed and forms dimers on the surface of a wide variety of cells (10). APN functions in digestion, angiogenesis, and synaptic activity and cleaves peptides bound to MHC molecules of antigen- presenting cells. Transfection of nonper- missive cells with hAPN is sufficient to confer susceptibility to HCoV-229E infec- tion (10). For the group 1 coronaviruses, early attempts at developing transgenic mice expressing the hAPN receptor failed to produce a susceptible model, suggesting that other cofactors might be essential for in vivo replication (14). This outcome is not unique to HCoV-229E; similar findings were reported in transgenic mice expressing the poliovirus and measles virus receptors (15). Although the fundamental basis for this dichotomy remains undetermined, modifications that enhanced virus growth in these models included the generation of doubletransgenic mice that also contained defects in innate immune responses, virus strain variation, or changes in the route of inoculation.
Future Directions
Lassnig et al.’s article (6) provides a para- digm for the generation of transgenic animals that are susceptible to HCoVs. SARS-CoV replicates efficiently in BALBc mice without significant clinical disease or pathology, limiting the useful- ness of this model for viral pathogenesis studies and the identification of virulence determinants (20). The development of human angiotensin-converting enzyme 2 transgenic animals may well serve as a more robust model for SARS-CoV. Im- portantly, hAPN humanized mice allow studies into HCoV-229E pathogenesis, tropism, replication, and spread in an immunocompromised host. hAPN is highly polymorphic in human populations, and the availability of this animal model al- lows investigation into whether allelic variation in the receptor inf luences HCoV-229E replication and pathogenesis in vivo, as has been so elegantly described for other RNA viruses like noroviruses (21, 22). The molecular basis for HCoV- 229E adaptation represents another rich avenue of investigation. Although the S glycoprotein may be critical, other genetic changes could equally contribute to in vivo replication, adaptation, and pathogenesis. Because virus entry and spread are often- times restricted by innate host defense mechanisms, it is likely that one or more mutations may evolve that restrict activa- tion of antiviral host genes in Stat/
mice. The molecular clone for HCoV- 229E provides the necessary tool for the identification and functional analysis of genetic elements responsible for in vivo adaptation and pathogenesis.
Murine models for HCoV-229E and SARS-CoV infection provide a means to study viral vector tropism and the efficacy and biosafety of HCoV-based vaccine vectors. The coronaviruses’ unique genome organization and replication strategy allow simultaneous regulated expression of multiple foreign genes from transcription regulatory sequences encoded at the 3 end of the genome. Coronavirus vectors can be targeted to different species, tissues, and mucosal compartments allowing for directed gene expression. It is likely that several kilobases of foreign genetic material can be stably incorporated and expressed in coronavirus genomes. HCoV vectors can be designed to safely target payloads to specific tissues or organs (13). The achievement by Lassnig et al. (6) will encourage further studies into human coronavirus replication and pathogenesis in vivo while simultaneously propelling the development of second-generation animal models for applying coronavirus-based vaccines and therapeutics in the treatment of human diseases.
