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2016年4月11日星期一

HIV shows its resistance to gene scissor

There is new evidence showing that HIV is fickle and difficult to cure. Chinese and Canadian scientists published an article in the American journal Cell Report on the 7th reporting that the HIV now can also soon show resistance response to the popular "gene scissors" therapy, but this therapy is still expected to be improved to continue to be anti-AIDS.

Scientists discovered that bacteria can obtain partial DNA (deoxyribonucleic acid) fragment and integrate it into the genome to form memory after a virus infection. When invaded again by this time, bacteria will transcribe corresponding RNA (ribonucleic acid) and use the "location information" therein to guide the locating and cutting of Cas protein complexes, thus destroying the invading virus DNA.

In recent years, the popular "gene scissors" therapy - genome editing technology CRISPR just uses this principle, using a customized RNA to lead Cas9 enzyme which acts as a role of scissor responsible scissors effect. Scientists cut the DNA viruses imported by HIV into host cells according to presupposed sites, thus preventing the proliferation of HIV replication.

But according to these new reports, their experiments confirmed that HIV can escape under gene scissors rapidly. The sequencing of the genome with HIV escape indicates that this virus had changed the DNA target sequence identified by CRISPR technology.

Liang Chen pointed out that the appearance of HIV's escape or a "resistance" is not accident. What surprised them was that further analysis showed that the changes of HIV were mostly not caused by virus reverse transcriptase which was generally considered by the scientific community. He thought the changes happened when host cells were trying to restore the cracked DNA because of cutting after Cas9 enzyme cut the DNA of HIV. "In other words, the therapy also helps in the escape of the virus when inhibiting the proliferation of HIV."

The researchers proposed two improved schemes to treat AIDS using gene scissors: one is to attack multiple HIV genomic sites to increase the difficulty of escape for virus; the second one is to use scissors enzyme except Cas9.

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2016年3月18日星期五

British research team firstly discovers the infection mechanism of HIV and Ebola virus

A research team led by the University of Leeds recently observed how the AIDS virus and Ebola virus attach to cells and spread the virus infection for the first time. The latest achievement of this study published in the Journal of Applied Chemistry is hopeful to provide a new method for the treatment of these diseases: blocking the interaction between the virus and cells, rather than eliminating the pathogens.

According to the report of the official website of University of Leeds, the lead author of this research paper, Dr. Yuan at Astbury structure Molecular Biology Center said that so far, the problem that how AIDS virus and Ebola virus attach to cells is still a "black box". Although scientists know that the virus can interact with healthy cells, in which way that they are bound together remains a mystery.

To do this, the researchers used is called "quantum dots" nano-crystals (about the size millionth of a millimeter), mimicking the shape of the virus, as the virus "double" experiment. Quantum dots are fluorescent crystals, color of light emitted depends on the size of its crystals, this property makes quantum dots is applied to a new generation of TV manufacturers, or as an advanced biological fluorescent probes for molecular and cellular imaging.

In order to be able to bind the quantum dot cells, as they must be wrapped in "sugar-coated." Paper co-author, Dr. Bruce Turnbull Astbury structure Molecular Biology Center said that all human cells were wearing "sugar-coated", their interaction with other cells by binding these proteins sugar; virus through the interaction between the protein and sugar attached to the surface of healthy cells, they want to find out what factors control the binding process.

The results showed that the two proteins that interact with the sugar on cell surface ——DC-SIGN and DC-SIGNR, bind with the surface sugar of AIDS virus and Ebola virus in different ways, thus resulting in the spread of the virus. While before this, the two proteins show different personalities like twins and are almost indistinguishable. The study will contribute to the ultimate development of a series of inhibitors designed to bind to specific virus.

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2016年2月23日星期二

The inrease of methylation that helps the HIV virus replicate

Researchers from the University of California, San Diego School of Medicine, found that HIV infected human immune cells can trigger the significant increase of a chemically modified human viral RNA - methylation, thereby helping the virus replicate. The study published in the February 22 journal Nature Microbiology establishes a new mechanism of the interaction between controlling HIV replication and the host's immune system.

Senior author of the paper, Dr. Tariq Rana, Professor, University of California San Diego School of Medicine, said: "Over the years we have a number of pharmaceutical companies and colleagues have been working on the development of targeted HIV genetic material --RNA drugs, but failed to push it into the clinical now we know the reason - we do not use these modified RNA target sequence to develop drugs, and the reality of RNA are different.”

In human cells, RNA is responsible to a command from the nucleus to the cytoplasm DNA the genetic material to go, in the cytoplasm of cells using these machine instructions to build proteins. In contrast, the entire HIV genome is composed of RNA rather than DNA constructed. The virus hijack the cellular machinery of the host to itself RNA translation into protein.

Cells can be controlled or change its function by chemically modifying RNA. One is referred to as N6- methyl adenosine (m6A) modified in humans and other organisms are common. In 2011, the Chinese chemical biologist Professor He Chuan the first to discover, the first can be reversed most common mRNA methylation modification: N6- methyl adenosine (m6A) of RNA demethylase, certificates and DNA and protein seen as adding and removing the methyl group can significantly affect these messenger RNA, and gene expression. June 2015, Professor He Chuan m6A reveals a new feature: the regulation of messenger RNA (mRNA) translation efficiency. These groundbreaking findings published in the journal Cell. October 2015, Samie R. Jaffrey Cornell University who led the research team published an article that, mRNA 5 'UTR of the RNA methylation (m6A) does not depend on the hat can promote protein translation in the journal Cell.

But until now people for m6A in the human immune system, as well as in our cells and invading pathogens such as HIV interaction between the roles is poorly understood.

In this study, Rana research team first discovered m6A modifications in HIV RNA. They also studied the infection of human immune cells during m6A for HIV RNA and function of the human host.

The first author of the paper, Rana laboratory Gianluigi Lichinchi graduate student, said: "People always thought m6A is a stable cell RNA modification of new studies confirms it is very dynamic, fast response to external stimuli such as viral infections in the future, these studies. The discovery could help improve and enhance HIV / AIDS vaccine design and efficacy."

Rev protein of HIV RNA is encoded by the gene. When constructed Rev protein in the cytoplasm of human host cells, they will return to the nucleus, where, Rev gathered on an HIV RNA known as Rev-responsive element (RRE) is a special site. Rev helped to transport the new generation of HIV RNA transcript into the host cytoplasm. This is an important step in viral replication.

The team is determined; m6A on human and viral RNA modification affects HIV Rev protein and RNA RRE interaction between. When the researchers responsible for silencing removed from the RNA enzyme m6A, HIV replication increases. In contrast, when they were silent m6A add up to the RNA enzyme, HIV replication reduces - the researchers say can be used in pharmacological studies have found that to fight HIV infection.

Rana said, "Such modification in research in the physical structure and HIV RNA genome of HIV field over the past 30 years had been missed. If other viruses having RNA genomes also use this mechanism to escape m6A modified immune surveillance and control them, I wouldn't be surprised. These viruses include influenza virus, hepatitis C virus, Ebola virus and Zika virus and so."

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2015年12月30日星期三

An antibody that is a promising key to the prevention of infection by HIV

Proteins which are called broadly neutralizing antibodies (bNAbs) are a possible key to the reduction with contamination by simply HIV, the virus several AIDS. bNAbs happen to be obtained in blood vessels biological materials through a number of HIV sufferers in whose immune programs may the natural way handle the contamination. These types of antibodies may possibly protect the patient's wholesome debris by simply realizing the protein labeled the envelope surge, found on the surface area off HIV traces and inhibiting, and also neutralizing, the results from the malware. At this point Caltech experts have discovered any particular one distinct bNAb might possibly discover that signature bank protein, at the same time you will need on distinct conformations in the course of infection--making the idea simpler to be able to identify and reduce the effects of the infections inside the unhygienic patient.

The procedure with HIV contamination takes place if the malware happens into make contact with using individual immune debris labeled To debris that will have a particular protein, CD4, on their particular surface area. Three-part (and also "trimer") proteins labeled envelope spikes on the surface area from the malware discover and hole to the CD4 proteins. The spikes could be inside whether sealed and also the start conformation, heading through sealed to be able to start if the surge binds to be able to CD4. The start conformation after that activates fusion from the malware while using focus on cellular, allowing the HIV malware to be able to down payment its genetic stuff inside sponsor cellular, making the idea to get the factory to make different infections that can continue to be able to infect alternative debris.

The bNAbs discover the envelope surge on the surface area with HIV, and quite a few identified bNAbs simply discover the surge from the sealed conformation. Even though simply focus on with neutralizing antibodies is the envelope surge, just about every bNAb truly characteristics by simply realizing only one precise focus on, and also epitope, with this protein. A number of locates allow stronger neutralization from the malware, and, as a result, a number of bNAbs tend to be more helpful against HIV when compared with other folks. Inside 2014, Bjorkman and here collaborators during Rockefeller Collage reported first portrayal of an efficient bNAb labeled 8ANC195 from the blood vessels with HIV sufferers in whose immune programs may possibly the natural way handle their particular attacks. Additionally, they observed that this antibody may possibly reduce the effects of the HIV malware by simply focusing on an alternative epitope when compared with another earlier identified bNAb.

In the recent study published in Cell paper, the researchers precisely investigated how 8ANC195 functions--and precisely how its unique properties could be advantageous for HIV therapies.

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