A team of Harvard scientists has taken the first step to solve mystery about why HIV patients are more susceptible to TB infection.

According to USAID, 42 million people are HIV infected & almost one third of them are also TB infected. It is believed that HIV interferes with the cellular and molecular mechanisms used by the lungs to fight TB infection.

This mystery has been solved when scientists extracted immune cells called “alveolar macrophages” from the lungs of asymptomatic HIV +ve patients as well as healthy patients ” HIV –ve.” They observed a decrease in response towards TB bacterium in HIV +ve patients when compared to HIV –ve patients.

A further examination of lung specimens showed an increased level of a molecule called IL-10, which elevates the amount of a protein called “BCL-3″ in alveolar macrophages and this reduces their ability to ward off TB infection.

It seems that HIV increases severity of TB infection, where both represent two of the most significant health challenges in human history.

Source: Science Daily.

Image credits: The HIV replication cycle.

Tags: BCL-3, HIV, IL-10, TB, USAID

Researchers at Massachusetts General Hospital (MGH) are investigating a new way to block replication of hepatitis C virus “HCV” by targeting not the virus itself, but the genes that the virus exploits during its life cycle.

HCV has a high rate of replication that it can replicate a trillion particles per day. Also, due to its high rate of mutation, it can escape our immune system.

HCV replicates mainly within hepatocytes in liver by binding to receptors on the surface of the liver “CD81″ and human scavenger receptor class B1 “SR-BI”. Then it utilizes the intracellular machinery necessary for its replication.

Transmission occurs by blood to blood contact, where it causes chronic liver infection in about 70-80% of patients & long term infections can cause liver failure or liver cancer.

HCV infection is usually treated with a six to eleven month regimen combining peginterferon and the antiviral drug ribavirin, but unfortunately, treatment is not successful in many patients and has serious side effects that some cannot tolerate.

Many drugs target viral enzymes, but due to the great ability of HCV to mutate, such approach lead to the emergence of resistant strains.

Recently, a new strategy has developed, which is to block human genes, which act as a cofactors for HCV infection. Using small interfering RNAs (siRNAs), researchers examined blocking of approximately 21,000 predicted messenger RNA transcripts in the human genome.

The siRNA scan found 96 genes that appear to have a role in viral replication, one gene codes for an enzyme called PI4KA, which is believed to be involved in the formation of membrane structures within the cell. Another group of genes contribute to formation of the coat.

So, by blocking these genes, HCV replication is stopped. At this time, these tested agents might not be suitable for therapeutic use.

Source & Image credits : Harvard Science.

 

Tags: blood contact, CD81, HCV, hepatocytes, Massachusetts General Hospital, peginterferon, PI4KA, ribavirin, siRNAs, SR-BI

If you try to search in the library or over the internet for AIDS, you will find a huge amount of information available. You will also figure out that all scientists reach a dead end at the step of treating or vaccinating against AIDS. Their stop makes you never stop thinking: why can’t they continue? Why is there no cure for such a disease? Or at least why can’t they stop the progress of this illness by simply making a vaccine? It is like reading the same book millions of times without understanding its end, then you re-read the last chapters but still “YOU CAN’T”!!

I think that we need to restart reading the book from its beginning. We need to re-read about the origin of AIDS infections, to know more about HIV genome, and how its genes function; then we may know how to slow down or terminate progression of the virus inside the human body or at least to stop its passage from an individual to another. Hence, we may be able to read the book again and this time we can understand its end.

AIDS was initially reported on June 5th, 1981. But, it is more precise to mention the first documented AIDS case, which was in 1959. At that time, no one was able to define such an illness; however, scientists did a favor for the humankind by preserving the infected tissues till someone would be able to define HIV, i.e. after 1981. I may ask why not before 1959? But who can answer a question like this?

The origin of AIDS has so many controversial theories, including conspiracy theories. One of these is that HIV arose as a result of leakage in the US governmental or military labs during the development of a biological weapon. You may ask Dr. Leonard G. Horowitz (the author of Emerging Viruses: AIDS & Ebola. Nature, Accident or Intentional? And Death in the Air: Globalism, Terrorism and Toxic Warfare) for evidence to prove such an idea. As wikipedia page of ” AIDS origins opposed to scientific consensus” mentions his theory which claims that AIDS virus was engineered by such U.S. Government defense contractors as Litton industries for the purposes of bio-warfare and “population control”.

Dr. Alan Cantwell (the author of AIDS and the Doctors of Death) supported this theory, by naming one scientist that led the US military research on homosexual and bisexual men between 1979 and 1981; he attributed these research activities to Dr. Wolf Szmuness. And, when Dr. Alan was asked about the cases that were reported before 1979, his answer was that the American media masked the truth at that time! This has been also mentioned on “AIDS origins opposed to scientific consensus” Wikipedia webpage.

Another unreliable hypothesis had been advanced by Edward Hooper, as he accused Hilary Koprowski, the polish virologist and immunologist who was preparing polio vaccine using tissue cultures from non-human primates during 1950s, that he might have transferred AIDS from monkeys to human. This idea couldn’t be evidenced when one of these vaccine vials had been checked in 2000 to show negative HIV or SIV (Simian immune-deficiency virus that infects chimpanzees). Also, by checking the protocols of that old research, it is clear they were working on monkeys’ kidney cells that cannot transmit AIDS. But can one negative vial become a prove for the whole negativity?!

The most accepted and recent theory assumes that HIV is an evolution from SIV. This Cameroon Chimpanzees theory was suggested in 2006 after a study on genetic samples from more than 1300 chimpanzees within 7 years by Dr. Beatrice Hahn. It seems that one person had been bitten by one of these apes or got cut while he or she was trying to slaughter one of these animals, maybe for eating purposes!!

If this Chimpanzee in the picture is the main suspect now for HIV triggering on earth, the question now is: Do we have current reports for the same transmission from apes to human? If yes or no, I think we need to re-study and search that SIV which might tell us something about its “daughter” HIV (as accepted by most of the scientists). It is like reading the book from its beginning not the last chapters, sure it will tell us new things.. Like what? I really dont know, it may be like the first idea that led to inventing the nuclear bomb, would you believe me if I told you more than 60 years ago that there is an idea to bombard the nucleus to make a huge bomb? It was just an idea, but the know how was not known. I think it is the same for the AIDS book: we need to re-read but we still don’t know what is going to happen after that reading. All I know that we need to re-read with a new vision, not the same ordinary way of reading.

Image credits: http://upload.wikimedia.org/wikipedia/commons/8/8d/South_Djoum_Chimp.jpg

Tags: AIDS, AIDS origin, Cameroon Chimpanzees hypothesis, Consiperasy Theories, conspiracy theories, Dr. Alan Cantwell, Dr. Beatrice Hahn, Dr. Leonard G. Horowitz, Dr. Wolf Szmuness, Edward Hooper, Hilary Koprowski, HIV, SIV

Nothing is impossible..

Things, you think are absolutely harmful, may be highly beneficial if we use them in a new way.

Viruses can be used in the treatment of cancer, a field known as oncolytic virotherapy.

But can you imagine that they are safer & highly specific than other traditional chemotherapy???

You will get the key when you know that they destroy cancer cells with a high accuracy that scientists called them “magic bullet”.

Simply, the mechanism of most viruses is to infect our cells, then to use them as a factory to produce more & more viruses.

Viruses are highly specific, they replicate in cells having receptors for them. So, we need to change viruses to selectively bind to tumors.

In fact, a virus consists of a coat & genome.

So, we got two methods to generate tumor selectivity.

First: By making modification on viral coat in order to increase adhesion between coat & cancer cells “Transductional Targeting”.

Second: By altering viral genome, so it can only replicate in cancer cells “Non-Transductional targeting”.

However, many primary cancers were resistant to conventional virotherapy.

Researchers at McGill University and the affiliated Lady Davis Research Institute of the Jewish General Hospital, along with colleagues at the University of Ottawa and the Ottawa Health Research Institute (OHRI) have discovered that a family of compounds called histone deacetylase inhibitors “HDI” which convert oncolytic viruses into more potent weapon.

So, HDI can augment the ability of the virus to target & kill the cancer cells.

Many viruses can be used especially those with dsDNA
genomes “as adenovirus and herpes simplex virus” where they have a higher stability & less susceptible for mutations.

Researchers utilize Vesicular Stomatitis Virus “VSV” as it is not a human pathogen. So, most individuals don’t have antibodies against it & can be treated before they gain immunity.

Human trials have been already approved & the results of these experiments will determine if this viral bullet is really a “magic bullet”.

Source: ScienceDaily

Image credits: Vesicular Stomatitis Virus

Tags: cancer cells, histone deacetylase inhibitors, magic bullet, non-transductional targeting, traditional chemotherapy, transductional targeting, tumor selectivity, vesicular stomatitis virus

Did you ever think about only one disease that causes the death of 50 million people? and around a year!!!!

Unfortunately, it already happened between 1918-1919 and is known as Spanish flu.

Flu (influenza) is a highly contagious respiratory infection caused by influenza viruses, which are divided into three types A, B and C.

Type A influenza is the most frightening and epidemic.

Type B influenza  causes milder symptoms than type A.

Type C influenza tends to be mild and does not spark epidemics.

Type A flu virus is subdivided into subtypes based on two surface proteins, hemagglutinin (HA) and  neuraminidase (NA).

Now, Scientists know 16 HA subtypes and 9 NA subtypes of the flu virus.

A (H1N1) and A (H3N2) are the  subtypes of influenza A viruses found in people, and there are no subtypes of influenza B virus.

The influenza viruses contain eight segments of single-strand RNA ,  continually change over time through “antigenic drift” or “antigenic shift”.

So, there is new flu vaccine every year and from time to time we face a new flu outbreaks.

Now, there is real fear between scientists and people of transmission of influenza viruses from animals to people.

There is a promising trial of new flu vaccine , targeting the internal proteins of the virus, this vaccine may be used in vaccination of many viruses like flu in mechanism of infection. (you can see BBC report Here).

References :

Flu

What Is Flu?

Types of flu

Influenza virus

History of Flu Epidemics

The Influenza (Flu) Viruses

Types of Influenza Viruses

Flu Virus Can Change: “Drift” and “Shift”

For Further reading

Seasonal Flu

Flu Channel

Cold Channel

Bacterial Pneumonia and 1918 flu

Tags: 1918 flu, antigenic drift, antigenic shift, flu, flu outbreaks, hemagglutinin, influenza, neuraminidase, spanish flu, ssRNA, types of flu, vaccine

In an on-going study at the University of Rochester Medical Center, scientists have come across a new form of inheritance which would probably astonish Mendel himself. Research has shown that parents pass on the human herpes virus 6 “HHV-6″ to their offspring because the virus has integrated itself into the infected parent’s chromosomes. And it is actually not as odd as it sounds. One in every 116 newborns is affected by this unique congential infection. The virus appears to integrate itself into a position in the chromosome concerned with the maintenance of the body’s normal immune function.

Typically, HHV-6 causes roseola which is characterized by high fever, rash, and mild gastrointestinal symptoms. However, the number of viruses found in children, who carry the virus within their genes, is much higher than those who were infected merely through the placenta. 86% of the children included in the study had the virus integrated within their chromosomes. The HHV-6 DNA itself was found in a hair sample provided by one of the parents. Only six of the congenitally infected babies were infected by the mother through the placenta.

The odd part about this does not lay in the fact that the virus has integrated itself within the chromosomes, but that it was actually passed on. So far, the long-term consequences on the children’s immune system is unknown but to have a virus lying around like that in their DNA…simply frightening, yet fascinating.

Source: Biology News Net

Press release: URMC website

Original research paper: Chromosomal integration of human herpesvirus 6 is the major mode of congenital human herpesvirus 6 infection. Pediatrics. 2008 Sep;122(3):513-20. PMID: 18762520. (Vote for the abstract on Biowizard)

Tags: chromosomal integration, family, HHV-6, inheritance, virus

“It’s an honor to announce that we’ve successfully discovered, cloned & characterized the densonucleosis virus (DNV) Antigen, which will be able to infect Anopheles gambiae. That will hinder its ability to transmit Malaria parasite, Plasmodium or, at least, reduce its lifespan. I’ve to tell you this: This will be the latest in Malaria control.” Well.. those are my words but, of course, it is not my discovery. It’s the team of researchers from Johns Hopkins who discovered it. To realize how big it’s; we first need to know the previous approaches & trials in Malaria control.

To think, just think, about control/ prevention of any of those vector-borne parasites; automatically researchers think about these:
1- Prevent infection – disease – transmission.
2- By looking at: the parasite’s life cycle – the mosquito – the human immune system.
3- So, it’ll look like that: get humans vaccinated – develop genetically modified mosquitoes incapable of transmitting the parasite or simply “I was so naive to think that it’s simple” kill them with insecticides (anti-vector measures) – target the parasite at any stage of its life cycle.

For decades, DDT (dichloro-diphenyl-trichloroethane) & Chloroquine were successfully used in eradication of Anopheles & Plasmodium respectively, “I do like this word, makes me sound like a pro”. Chloroquine was used in treatment as well as prevention, till the emergence of chloroquine-resistant Plasmodium parasites and DDT-resistant Anopheles mosquitoes. Yes, they overcame the humans’ arsenal. So, preventing spread of resistant parasites is the #1 priority.

We can’t talk about all control strategies today, so we’ll talk about anti-vector measures. What do they use in control programs as anti-vector measures?
1- Insecticide-treated bednets (ITNs) & long-lasting ITNs (LLINs) it helped kids to survive. The only allowed insecticides to be used in ITNs are pyrethroid insecticides, so when the pyrethroid resistance emerged, as usual, it was really bad.
2- Indoor residual spraying (IRS) using DDT
One word about the mechanism of action of DDT & pyrethroids, both target voltage-gated Na-channels. So, when a set of mutations change the protein structure; Congratulations! It’s resistance to both DDT & pyrethroids.
3- New approach: Molecular talk; Know more about “blood meal” host selection. Yes, Anopheles smells the host, so researchers want to identify that pathway.
4- Another new approach: They are investigating genes which encode proteins that may interrupt the development of the parasite in the Anopheles.

The latest as an anti-vector measure is using Paratransgenesis or “the genetic manipulation of insect symbiotic (mutualistic, commensal or parasitic) microorganisms”, I can’t get the term or the definition. I’ll say it like that: “Any other m.o. has a relationship with the vector”. The steps are:
1- Know the Ag (Pick the gift)
2- Get the gene(s) engineered to be successfully expressed (Wrap the gift)
3- Delivery to Anopheles (Deliver the gift)
So the gift will be the non-enveloped ssDNA virus called (DNV). Its genome is very small, when they say for a viral genome that it’s small, so it has to be small (4–6 kb). The entire genome can be placed in a plasmid.

Back to the story of the discovery, they were doing a totally unrelated experiment when they found that strange band/ zone. They isolated it from the gel, cloned, sequenced, ran through BLAST which showed that it looks like DNV of Aedes aegypti (AeDNV) but not the man himself. They did multiple tests to identify the Ag, e.g. Immunofluorescence assay. There was a trial to infect Anopheles gambiae with DNV of Aedes aegypti which wasn’t successful in infecting adults from Anopheles gambiae. But the novel “AgDNV is highly infectious to An. gambiae larvae, disseminates to adult tissues, and is passed on to subsequent generations.”

Tags: AeDNV, AgDNV, anopheles gambiae, anti-vector measures, DDT, IRS, ITNs, malaria, paratransgenesis, plasmodium

Aethlon Medical has developed a new device called Hemopurifier® which acts a lot like the usual hemodialysis machine used in patients with end-stage renal disease but targets a different kind of particle within the blood, it captures viruses! The machine uses thin filters to capture & remove viruses from the blood. This requires an artery to act as an entry point of the blood to the machine, where it is filtered, and then sent back to the body, only cleaner.

The whole blood circulation passes through the machine almost once every 8 minutes. The entire process itself requires a few hours. Needless to say, this might prove to be revolutionary in the treatment of all sorts of viral infections: measles, mumps, hepatitis, west-nile virus, smallpox, HIV, avian flu, even the seemingly harmless human flu..just to name a few.

The device has already received a lot of attention & was in fact awarded. In a pre-clinical study, an astonishing 99.4% of H5N1 flu virus, as verified by real-time PCR,  was eliminated from the patient’s blood within an operating time of 6 hours.

This state-of-the-art device functions through using antibodies to capture viruses & toxins before their actual attack on the human organs. Patients can even be started on the machine before the physicians find out the cause of the disease. 

Source: ScienceDaily

Tags: blood, H5N1, hemopurifier, HIV, immunotherapy, virus

You may remember HBV, the famous hepatitis virus with its partially double-stranded circular DNA genome. I always wondered: What is that supposed to mean?! HBV has a very complicated replication cycle. I’m pretty sure that all molecular biology fans will be totally thrilled by reading this.

HBV replication cycle is divided into 3 stages:

1- The infectious virion containing the partially double-stranded circular DNA, they call it RC-DNA (relaxed circular).

2- Right after the infection, inside the host nucleus, the genome becomes cccDNA (covalently closed circular DNA). It looks just like plasmids. HBV needs that highly stable form because it’s a chronic infection; it doesn’t want to be lost during host cell division. It may be still there in the host cells even after effective antiviral therapy.

3- Finally transcription takes place, several RNA molecules are produced, some of them are genomic (contain the whole genome) named pgRNA (pregenomic RNA) & some are subgenomic (encode needed enzymes) It uses the cell’s RNA polymerase II to do all this.

So, what happens to the pgRNA? They get inside progeny capsids ready to be reverse transcribed with the help of P protein (Its reverse transcriptase) which is “co-packed” in the pgRNA- progeny capsid package to get it back to the RC-DNA. Then the mature RC-DNA containing-nucleocapsids could undergo cccDNA amplification, or could be enveloped & ready for release from the cell. Of course all this is in equilibrium; if there’s only one copy in the cell, the priority is not to make cccDNA but to be enveloped & released.

Why the RC-DNA needs to be first cccDNA before transcription? As I got from this review, the RC-DNA has the normal (-)-strand (opposite sense to mRNA) but its complementary, the (+)-DNA strand, is not in full length. It results from the non-identical nucleotides supply; because the envelop is impermeable to nucleotides. At the 5′ end of the (-)-strand, there’s the P protein. But at the 5′ end of the (+)-strand, there’s some RNA nucleotides remains from the pgRNA…It was its primer, remember? All these are removed to be a cccDNA. The P protein may has a role in completing the (+)-strand.

Image credits:
Hepatitis B Virus Replication: http://www.meds.com/

Tags: cccDNA, HBV, P protein, pgRNA, RC-DNA, reverse transcription

Scientists are harvesting all of them potatoes for an investigational experiment is being done on patients with Alzheimer’s disease using protein extracts obtained from a potato virus.

Alzheimer’s is associated mainly with amyloid plaque within the neurons of the brain. A major portion is formed of beta amyloid which should, in normal cases, break down on its own but rather tends to accumulate forming the insoluble hard plaque. Here is where the potatoes pitch in.

A fairly known potato virus “PVY“, basically harmless to humans, which I & probably you might have been previously exposed to, contains an amyloid-like protein. Through isolating the potato virus & injecting it in experimental animals with booster doses every month, the levels of antibodies against the protein, in 4 months, quickly rose to an extent that allowed these animals to successfully fight the formation of beta amyloid plaques, a contributing factor in the progression of Alzheimer’s disease.

Surprisingly, the mice also developed AD antibodies even when given PVY-infected potato leaves. Research on human subjects has been postponed for fear of the development of autoimmune encephalitis, although the early trials have been very promising.

Hopefully, this debate will soon be over once a purified version of the virus safe enough for human use is prepared & tested on these patients. Might be just a new ‘awakening’

Tags: alzheimer's, amyloid, food, potato