Antígenos quiméricos y Mutación del DNA

Estefanía Orozco BetancurMedical student third semester

Cancer fighting gene immunotherapy shows promise as treatment for HIV and Viruses

revealed to be a major driver of human evolution

Medical utility

Learn different innovative mechanisms that have been discovered to solve the treatment problems due to the viral replication in HIV

Recognize the importance of protein adaptation within the evolution and it’s protection mechanism against virus attack.

Impact in quality health of people that are affected by different diseases related to virus infection.

Balance the cost-effective implications in these recently discovered treatments and the probability to implement them in a clinical trials.

References

• Journal reference:David Enard, Le Cai, Carina Gwennap, Dmitri A Petrov. Viruses are a dominant driver of protein adaptation in mammals. eLife, 2016; 5 DOI: 10.7554/eLife.12469

• Genetics Society of America. "Viruses revealed to be a major driver of human evolution: Study tracking protein adaptation over millions of years yields insights relevant to fighting today's viruses." ScienceDaily. ScienceDaily, 13 July 2016. <www.sciencedaily.com/releases/2016/07/160713100911.htm>.

• Journal Reference:Ayub Ali, Scott G. Kitchen, Irvin S. Y. Chen, Hwee L. Ng, Jerome A. Zack, Otto O. Yang. HIV-1-Specific Chimeric Antigen Receptors Based on Broadly Neutralizing Antibodies. Journal of Virology, 2016; 90 (15): 6999 DOI: 10.1128/JVI.00805-16

• University of California - Los Angeles Health Sciences. "Cancer-fighting gene immunotherapy shows promise as treatment for HIV: Artificial receptors kill cells infected with the virus that causes AIDS, study finds." ScienceDaily. ScienceDaily, 15 July 2016. <www.sciencedaily.com/releases/2016/07/160715171315.htm>

• Viruses revealed to be a major driver of human evolution

• Cancer fighting gene immunotherapy shows promise as treatment for HIV

Estefania Orozco BetancurMedical Student Third semesterTeacher: Lina Martínez

Agosto 22 de 2016

http://dx.doi.org/10.7554/eLife.12469

http://dx.doi.org/10.1128/JVI.00805-16

Introduction

In this brochure you will be informed about the latest advances in virus and retrovirus mechanisms of action and new therapies to resolve secondary effects that affect health such as in HIV, on the other hand, a pattern relationship between the protein interaction with viruses within the cell structure and the evolution has been established and is promising to discover and select wich proteins may be specific to attack the virus mechanisms in order to protect the cell, therefore the body.

Cancer fighting gene immunotherapy shows promise as treatment for HIV

Investigators realized that recently discovered potent antibodies could be used to create a type of cell called chimeric antigen receptor (CARs) to be used to kill cells infected with HIV-1. The relevance in terms of these created immune T cells (CARs) relies in the specific membrane receptors that are designed to kill specific cells containing viruses or tumor proteins, these receptors are the main research in the use of gene immunotherapy as a solution to fight cancer, or on the other hand to make the immune system a tougher or stronger one, the main battle with virus in the organisms is the capacity of these to hide from the immune system and their rapid response like in aspects such as replication. To explain in simple terms the basis of the investigation was to create artificialTcell receptors and reprogram killer T cells to kill HIVinfected cells using seven recent studied “broadly neutralizing antibodies” that act as binding receptors to multiple strains of invading viruses, what is interesting is that all of them have different degrees of affinity of interaction with the killer cells to make them proliferate, kill and suppress viral replication in response to the HIV infected cells

Opinion This study implicates a big impact within HIV treatments, which are at this point relying only on the control of the symptoms and this implicates a huge change in the objective of these treatments it’s promising because it would act in an important aspect, that is prevention and defense before, during and after to reinforce the immune system from all the virus attacks, and this research points out a few broadly neutralizing antibodies but it is a head start for many other investigations to determine more possibly receptors or pathways as solutions to the same common problem, HIV.

Viruses revealed to be a major driver of human evolution

“ Study tracking protein adaptation over millions of years yields insights relevant to fighting today’s viruses” Millions of years ago viruses have coexisted with many organisms, determining a competitive relation between themselves and this has had an impact within the evolution, investigators have realized that 30 percent of all protein adaptions since humans differentiation with chimpanzees have been driven by viruses, this explains the adaptation mechanism. This means that proteins that relay in our cells have the power to change in composition and shape as a form of adaptation to prevent the effects of viruses related to replication changes in the cell structure and function.

What investigators seek from now on is to find out which parts of the cell developed in the past a defense mechanism or shield against viruses to use these strong parts of the cell for investigation and conclude which proteins can be promising for the use in therapies. The main conclusion is that virus interactions with the cell have determined the pressures that made us what we are, and this is explained by the way virus introduces itself and takes over the organism’s cells to replicate and create a machinery and the misteries that rely are the different mechanisms or paths that viruses have to perform identical cellular functions, like DNA replication or membrane production.

OpinionThis study implicates a relevant task within human health because with the understanding and revelation of the mechanisms of interaction between viruses and cells, this can lead to one of the most important solutions in health, which is the prevention of all type of diseases related to viruses, that today have only treatment within symptoms (some of them like HIV) but others still rely a mystery.

Introduction

In this brochure you will be informed about the latest advances in virus and retrovirus mechanisms of action and new therapies to resolve secondary effects that affect health such as HIV, on the other hand, a pattern relationship between the protein interaction with viruses within the cell structure and the evolution has been established and is promising to discover and select wich proteins may be specific to attack the virus mechanisms in order to protect the cell, therefore the body.

Scientists recently discovered a very important relation between the cell mechanism of protection aganist viruses throughout time and the way different species have evolutionated to attack new diseases caused by virus processes, now what’s important is the determination of these experiments to uncover all the mysteries that are still present towards how to combat many pathways that viruses implement within the cell structure.

Other scientist have related immunotherapy as a promising solution for HIV, by using recently discovered antibodies and use them as antigen receptors to program them to attack cells that are infected with HIV

Introduction


“Investigators realized that recently discovered potent antibodies could be used to create a type of cell called chimeric antigen receptor (CARs) to be used to kill cells infected with HIV-1” The relevance in terms of these created immune T cells (CARs) relies in the specific membrane receptors that are designed to kill specific cells containing viruses or tumor proteins, these receptors are the main research in the use of gene immunotherapy as a solution to fight cancer, or on the other hand to make the immune system a tougher or stronger one, the main battle with virus in the organisms is the capacity of these to hide from the immune system and their rapid response like in aspects such as replication To explain in simple terms the basis of the investigation was to create artificial Tcell receptors and reprogram killer T cells to kill HIVinfected cells using seven recent studied “broadly neutralizing antibodies” that act as binding receptors to multiple strains of invading viruses, what is interesting is that all of them have different degrees of affinity of interaction with the killer cells to make them proliferate, kill and suppress viral replication in response to the HIV infected cells Opinion This study implicates a big impact within HIV treatments, which are at this point relying only on the control of the symptoms and this implicates a huge change in the objective of these treatments it’s promising because it would act in an important aspect, that is prevention and defense before, during and after to reinforce the immune system from all the virus attacks, and this research points out a few broadly neutralizing antibodies but it is a head start for many other investigations to determine more possibly receptors or pathways as solutions to the same common problem, HIV.

As said before the aim of this investigation was to implement 7 studied antibodies that act as binding receptors for viruse, on the other hand investigators created artificial immune T cells named CARs (chimeric antigen receptor) that use specific receptors and reprogram them to kill the cells that are infected with HIV, what is interesting is that all of the antibodies that act as binding receptors have different degrees of affinity of interaction with the killer cells and activate them in diverse ways to respond and supress viral replication in response to the HIV infected cells.

A previous research was done with unsuccessful results because the proteins that were used weren’t antibody-like. The only task from now on is to take this promising in vitro research and find the ways to implement the same mechanism of action in human cells, which implicates a deeper study within the implantation of these receptors and their adaptation to the human cell membrane including all its properties


Illustration of components

of second and third

generation chimeric antigen

receptor T cells

Picture taken fromhttp://www.cancer.gov


THERAPY

7 “Broadly Neutralizing antibodies “

Create chimeric antigen receptors (CARs)

Kill cells infected with HIV


Interesting Facts

Antibodies that act as binding receptors to multiple strains of invading viruses have

DIFFERENT DEGREES OF AFFINITY of interaction with killer cells

Therefore they all have different impact on the suppresion of viral replication

What’s next ?

Keep searching for

antibodies with the

most affinity therefore the most potent supressing

action


The main task from now on

is ...

Take this promising IN VITRO research

Investigate more and find the

mechanisms of action in human

cells

Deeper study of the implantation of these receptors within the

different cell membranes

Analize the cost-effective benefits and balance how

productive the therapy can be

Student Observation

This investigation implicates a huge impact in HIV treatments due to the main objective that is the

attack of the HIV mechanism of action in cells, it’s a promising treatment because it’s aimed to not only treat the second effects (which today’s treatments are based on) but attack directly the target of the

problem; virus replication


“ Study tracking protein adaptation over millions of years yields insights relevant to fighting today’s viruses” Millions of years ago viruses have coexisted with many organisms, determining a competitive relation between themselves and this has had an impact within the evolution, investigators have realized that 30 percent of all protein adaptions since humans differentiation with chimpanzees have been driven by viruses, this explains the adaptation mechanism. This means that proteins that relay in our cells have the power to change in composition and shape as a form of adaptation to prevent the effects of viruses related to replication changes in the cell structure and function.

What investigators seek from now on is to find out which parts of the cell developed in the past a defense mechanism or shield against viruses to use these strong parts of the cell for investigation and conclude which proteins can be promising for the use in therapies. The main conclusion is that virus interactions with the cell have determined the pressures that made us what we are, and this is explained by the way virus introduces itself and takes over the organism’s cells to replicate and create a machinery and the misteries that rely are the different mechanisms or paths that viruses have to perform identical cellular functions, like DNA replication or membrane production. Opinion

This study implicates a relevant task within human health because with the understanding and revelation of the mechanisms of interaction between viruses and cells, this can lead to one of the most important solutions in health, which is the prevention of all type of diseases related to viruses, that today have only treatment within symptoms (some of them like HIV) but others still rely a mystery.


“Virus interactions with the cell have determined the pressuress that made us what we are”

Now this explains the relevance of the study by indicating how the viruses had made us tougher indirectly by confronting our cells and determining the adaptation mechanisms

What is really interesting is that there has been found a pattern that determines only 2 responses to a massive virus implication such as pandemics and epidemics, that results in the adaptation or the extinction


Innovation within this

investigation

The discovery not only implicates proteins that are

related to the immune system; which is the most logical place to expect viruses to adapt, but also

any type of proteins that have contact with viruses can

participate in the adaptation mechanism against them


One of the main steps within this study was the establishement of a genomic database that included a comparison between 1,300 proteins of interest; meaning the ones that interact directly with the viruses and other proteins in the organism and concluded that the adaptations occured 3 times more frequently in the listed proteins than the others.


The main misteries that rely are the different mechanisms or paths that viruses have to perform

identical cellular functions , such as DNA replication or membrane production, the objective is the

understanding of these pathways to reveal different diseases that affect the present and future population

Student Observation

This study is really important because it gathers all the information and represents a contrast in what was

thought before about viruses, as new agents that appear and attack causing numerous diseases, now we have a strong base; evolution that determines how cells have resisted for millions of years and have strengthen the

ADAPTATION MECHANISM

Medical Utility

Learn and investigate the mechanisms of

action of diverse viruses and influence health

quality lifestyle of people suffering any

virus disease, therefore we are closer to

uncovering solutions that may lead to

advanced treatments

Develop prevention methods, to block certain targets that may be more

probable or sensible to virus actions

Medical Utility

• Impulse investigation to determine wich are the specfic proteins that are most implicated in the viral interaction and experiment in vitro to discover many other elements such as receptors, enzymes, factors that may be correlated.

• This may be the solution to prevent epidemics and pandemic expansion of any disease

• Investigations such as these may permit a comparison analisis of the reactions caused by viruses in the past and how modifications today impact on those effects ( are they better, worse, have they changed)

• Balance the cost-effective implications in these recently discovered treatments and the probability to implement them in a clinical trials.

• Impact in quality health in people that are suffering any virus related disease

Medical Utilty

Picture taken from:http://

www.prnewswire.com

• Learn the importance of the evolution pattern that was found between protein and viruses in

adaptation mechanism

• Recognize that cell reprogramation and creation of molecules that have the capacity to interact in a pathway causing a disease are promising

solutions, therefore they also implicate a deeper study within how to incorporate these artificial molecules and make them function in

an adecuate manner so the interaction with membrane receptors is viable, therefore their

action is as well.

Medical Utility

Picture taken from: http://www.labroots.com

REFERENCES

• Journal reference:David Enard, Le Cai, Carina Gwennap, Dmitri A Petrov. Viruses are a dominant driver of protein adaptation in mammals. eLife, 2016; 5 DOI: 10.7554/eLife.12469

• Genetics Society of America. "Viruses revealed to be a major driver of human evolution: Study tracking protein adaptation over millions of years yields insights relevant to fighting today's viruses." ScienceDaily. ScienceDaily, 13 July 2016. <www.sciencedaily.com/releases/2016/07/160713100911.htm>.

• Journal Reference:Ayub Ali, Scott G. Kitchen, Irvin S. Y. Chen, Hwee L. Ng, Jerome A. Zack, Otto O. Yang. HIV-1-Specific Chimeric Antigen Receptors Based on Broadly Neutralizing Antibodies. Journal of Virology, 2016; 90 (15): 6999 DOI: 10.1128/JVI.00805-16

• University of California - Los Angeles Health Sciences. "Cancer-fighting gene immunotherapy shows promise as treatment for HIV: Artificial receptors kill cells infected with the virus that causes AIDS, study finds." ScienceDaily. ScienceDaily, 15 July 2016. <www.sciencedaily.com/releases/2016/07/160715171315.htm>.



