Rhinovirus sequenced , 15 groups

[gsgs]

http://www.world-science.net/otherne...212_rhinovirus








Wikipedia:
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Rhinovirus (from the Greek rhin-, which means "nose") is a genus of the Picornaviridae family of viruses. Rhinoviruses are the most common viral infective agents in humans, and a causative agent of the common cold.
Rhinoviruses have single-stranded positive sense RNA genomes of between 7.2 and 8.5kb in length.

Rhinoviruses are composed of a capsid, that contains four viral proteins VP1, VP2, VP3 and VP4.[2][3] VP1, VP2, and VP3 form the major part of the protein capsid. The much smaller VP4 protein has a more extended structure and lies at interface between the capsid and the RNA genome. There are 60 copies of each of these proteins assembled as an icosahedron. Antibodies are a major defense against infection with the epitopes lying on the exterior regions of VP1-VP3.

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Rhinoviruses cause colds in an estimated 30 to 35 percent of all adults
more than 200 specific viruses that can cause the common cold have been identified.
Rhinoviruses cause up to 40 percent of colds, and this virus family has at least 100 distinct virus types in its group
Other important upper respiratory virus families are named coronavirus, adenovirus and respiratory syncytial virus.

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genbank:
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Human rhinovirus A (580)
Human rhinovirus sp. (551)
Human rhinovirus B (230)
Human rhinovirus C (80)
Human rhinovirus QPM (52)
Human rhinovirus 2 (27)
Human rhinovirus 89 (14)
Human rhinovirus 82 (14)
Human rhinovirus 14 (13)
Human rhinovirus 6 (13)
Human rhinovirus 3 (13)
Human rhinovirus 69 (11)
Human rhinovirus 37 (11)
Human rhinovirus 48 (10)
Human rhinovirus 17 (10)
Human rhinovirus 12 (10)

Human rhinovirus strain Hanks (4)
Human rhinovirus 263 Berlin 2004 (2)
Untyped human rhinovirus OK88-8162 (1)
Human rhinovirus NY-041 (1)
Human rhinovirus NY-063 (1)
Human rhinovirus NY-1085 (1)
Human rhinovirus NY-042 (1)
Human rhinovirus NY-060 (1)
Human rhinovirus NY-003 (1)
Human rhinovirus NY-028 (1)
Human rhinovirus W1 (1)
Human rhinovirus W6 (1)

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http://images.google.com/imgres?imgu...G%26ie%3DUTF-8

nonenveloped,30nm

The route of entry for rhinovirus is via the upper respiratory tract. The virus generally gets into the nasal passage through inhalation of particles or touching of the nose with a contaminated hand. Whithin the next 10-15 minutes, it is transported to the back of the throat. Once there, the virus attaches to cell surface receptors known as Intercellular Adhesion Molecule- 1 (ICAM-1), and infection begins. Rhinovirus is amazingly efficient at producing infections. It has been shown that 95% of people exposed to a rhinovirus strain they have not previously encountered become infected, and 75% of those infected become ill.
The infection remains localized in the upper respiratory tract. This occurs for one very important reason: rhinoviruses are extremely inefficient replicators at temperatures above 33°C. The virus may find its way to the lower portion of the lungs, but temperatures there will be several degress warmer (approximately 37°C) and will not be conducive to rhinoviral infection. The virus will also be swallowed and it will end up in the stomach where both increased temperature and decreased pH will work to prevent infection. Unlike poliovirus, the rhinovirus capsid (protective protein coat) irreversibly disassembles at low pH, effectively inactivating the virus.

[Laidback Al]

text from gsgs link in the post above . . .

Researchers cracking code of the common cold

Feb. 12, 2009
Courtesy University of Maryland Medical Center
and World Science staff

Scientists say they have put together the pieces of the genetic codes for all known strains of the pathogen responsible for the common cold, in work that might eventually lead to the first cure for the illness.

Model of the outer structure of the human rhinovirus. (Courtesy Jean-Yves Sgro, U. of Wisconsin-Madison)
Researchers at the University of Maryland School of Medicine and the University of Wisconsin-Madison completed the genomic sequences of many strains of the virus, called the human rhinovirus, and assembled them into a “family tree” showing their relationships. The study appears in the Feb. 12 online version of the journal Science.

“There has been no success in developing effective drugs to cure the common cold, which we believe is due to incomplete information” about the genes, said the study’s senior author, Stephen B. Liggett of the University of Maryland School of Medicine.

“We generally think of colds as a nuisance, but they can be debilitating in the very young and in older individuals, and can trigger asthma attacks at any age. Also, recent studies indicate that early rhinovirus infection in children can program their immune system to develop asthma by adolescence,” said Liggett, a pulmonologist and molecular geneticist.

The researchers found that human rhinoviruses are organized into about 15 small groups that come from distant ancestors. The discovery of these multiple groups explains why a “one-drug-fits-all” approach for anti-viral agents doesn’t work. But, said Liggett, “Perhaps several anti-viral drugs could be developed, targeted to specific genetic regions of certain groups. The choice… would be based on the genetic characteristics of a patient’s rhinovirus infection.”

Liggett added that while anti-virals seem the best bet, “the data gathered from these full genome sequences gives us an opportunity to reconsider vaccines as a possibility.”

The analysis found that some human rhinoviruses result from the exchange of genetic material between different strains of the virus in one person. The viruses also mutate often, helping them avoid being hunted down by the immune system, according to Liggett.

“As we begin to accumulate additional samples… it is likely that hotspots for mutation or recombination [gene exchange] will become apparent” within the viral genome, said the study’s lead author, biochemist and virologist Ann C. Palmenberg of the University of Wisconsin-Madison. “This will provide clues as to how flexible the virus is” in its survival strategies.

Human rhinovirus is believed to cause half of all asthma attacks and is a factor in bronchitis, sinusitis, middle ear infections and pneumonia. The coughs, sneezes and sniffles of colds are estimated to cost the U.S. economy some $60 billion annually.

Before this project, the genomes of only a few dozen rhinoviruses had been sequenced from a frozen collection of 99 different rhinovirus strains taken from patients over more than two decades. The study by Palmenberg and colleagues adds 80 genome sequences to this “library” and 10 more acquired recently from people with colds. During the study, several other research groups began to report the full genomes of some of the viruses in the previous collection, as well as some odd rhinovirus-like strains.

“Now we can put together many pieces of the human rhinovirus puzzle to help us answer some fundamental questions,” Liggett said: “how these rhinoviruses might mutate as they spread from one person to another; which rhinoviruses are more associated with asthma exacerbations and why rhinovirus exposure in infancy may cause asthma later in life. With all this information at hand, we see strong potential for the development of the long-sought cure for the common cold.”

[miso]

Originally Posted by Laidback Al

“There has been no success in developing effective drugs to cure the common cold, which we believe is due to incomplete information” about the genes, said the study’s senior author, Stephen B. Liggett of the University of Maryland School of Medicine."

Perhaps Liggett should have qualified his statement because a cure for the common cold is already in clinical trials and it didn't need his research.

Would that take the shine off the media hype? Sure would!

"Rhinoviruses access nasal cells by attaching to a receptor on the cell surface. Canyon-like clefts on the surface of the virus attach to the receptor and allow the virus to infect the cell. Biota is developing antiviral compounds which are designed to bind to these evolutionarily conserved clefts of HRV's capsid shell and interfere with virus attachment to the targeted cell's receptor.."

Source:http://www.biota.com.au/?page=1021001&subpage=1021018

Biota completed Phase I (single & multi-dose) clinical trial of its HRV drug, BTA798 in 2007 and is currenty conducting Phase IIa trials.

Never let the facts get in the way of an (American success) story.

[gsgs]

I also noticed this, that research is more likely to be mentioned
in newspapers or magazines when people or organizations
from the same country are involved.

This shouldn't hold so much for science journals
let alone pubmed.


Are you from Australia, BTW. ? (Biota=Australia)

[lili]

Traduction machine


The genome of all the known stocks is decoded

The virus of the cold exposed



In the crucial to bore the mysteries of the rhinovirus, the principal agent of cold but such a responsible projection d' lower respiratory infections and of asthmatic crises, of the American researchers determined the genetic sequence of all the known stocks of the rhinovirus (a hundred). Their analysis specifies the molecular characteristics of the many varieties of the rhinovirus, and gets a platform to include/understand their evolution and their weak points. This powerful tool will be invaluable for the future epidemiological studies like for the development of antiviral drugs or, which knows, of a vaccine.

OF OUR CORRESPONDING

The RHINOVIRUS is the principal agent of the banal cold (or rhinitis), but also a cause of rhinosinusite, of otitis, of lower respiratory infection, and of 50% of exacerbations Of asthma. It can also direct the immune system of the infant towards a asthmatic phenotype. It is estimated that each year the adults have between 2 to 4 colds and the children of school age can have jusqu' of it; to 10. The direct and indirect costs of the cold and its complications at the asthmatic ones are estimated at 60 billion per annum in the United States.
The traditional methods of culture and sérotypage of the human rhinovirus (RVH), a virus with ARN of the family of the picornavirus and close to the entérovirus, had identified 99 stocks of RVH. They were classified, on the d' basis; a partial sequencing, in two species: RVH-A (74 stocks) and RVH-B (25 stocks); they were also divided into 2 groups according to the cellular type of receiver used: either ICAM-1 (“major” group, 65 RVH-A and 25 RVH-B) or LDLR (“minor” group, 9 RVH-A). Recently, of new molecular tools aiming at identifying viral genomes “unknown” allowed d' to identify a new species of rhinovirus not yet cultivated, RVH-C, spread in the world and being able to generate more severe respiratory forms.
The genomic sequence supplements majority of the stocks had not been given yet. In order to define l' extended and the nature of the diversity of the RVH, and to better include/understand their evolution, of the researchers of the university of Wisonsin (Madison), Craig To be windy Institute (Rockville) and of the university of Maryland (Baltimore), completed sequence the genomes of the 99 original stocks (including 80 new complete genomic sequences), of 10 samples recently collected and 7 stocks of RVH-C.

A mine of information.

Starting from the sequences, the researchers built a lighting phylogenetic tree the evolution of the genomes. The rhinoviruses are organized in 15 small groups which come of remote ancestors.
The examination of the genomes reveals reasons preserved between all the stocks and of the sequences and specific structural elements of species - has, B, C and perhaps a new species D.
The sequence IRES (Internal Ribosome Entry Site) of the rhinovirus, able to initiate the translation in a way independent of the cap, is preserved and shows a specific configuration which could explain the fast translation of the ARN rhinoviral out of viral proteins.
This information could suggest a therapeutic approach. In analogy with the poliovirus, a segment 5' UTR hypervariable could affect virulence.
The researchers also discovered multiple changes (jusqu' to 800 distributed in all the genome) in the viral samples recently taken among caught cold patients, compared to 99 older stock of reference. Certain viruses transfer by modifying proteins slightly in order not to be destroyed by the antibodies of the patient.

The proof of recombinations.

They also found the proof of repeated historical recombinations of the genome, be-with-to say the exchange genetic material between 2 stocks distinct from the virus infecting the same person. “The capacity of the various stocks of the rhinovirus to exchange their genes and to form entirely new stocks was supposed not to exist”, note Dr. Claire Fraser-Liggett, professor of medicine and microbiology with theuniversity of Maryland, and member of the equip. “It is possible that can lead to the emergence d' a new stock of rhinovirus having dramatic properties”.
However, with the sequences of the rhinoviruses available, and a certain idea in the way in which they exchange their genes, it could be possible to predict the pathogenic potential d' a virus and to develop antiviral agents against l' infection. “While the antiviral ones are likely the most to be born, notes Dr. Stephen Liggett, the information collected starting from the complete genomic sequences give us l' occasion to reconsider the d' possibility; a vaccine, in particular by collecting multiple samples and by séquençant their genome. This work is in hand”.

http://flutrackers.com/forum/showthread.php?t=84150

[ironorehopper]

Pleconaril is perhaps one of the handful of chemical compounds able to partially inhibit Rhinoviruses.

Luckily, this drug never reached the market and it is only available for severe enteroviral infections, as investigational drug and for future prophylaxis should these viruses evolve in an unexpected way.

[miso]

Originally Posted by gsgs

Are you from Australia, BTW. ? (Biota=Australia)

In my endless quest to avoid flu season, I live six months in Australia and six months in Greece.

[gsgs]

do they reassort as flu does ?
how many point-mutations per year ? (as compared with flu)

homologuous recombination ?
how different can strains be while still recombining or reassorting ?

preferrably only within one of the 99 groups ? Or interchange
between different groups ?

[gsgs]

colds can often be used to study how viruses spread.
They can even infect human volunteers with colds,
but usually not flu for ethical reasons.

The spread in the air should be similar, but not survival.

flu is enveloped, rhino not, flu is 100nm,rhino only 30nm,
flu is polymorphic.
But in droplets they should spread similarly, I assume.

single viruses are too small to settle, I assume they would
just fill the atmosphere almost randomly ... but die
after a while depending on the conditions.

how many dead or alive cold-viruses are in our atmosphere ?



1e14 cells in a human,
adenovirus : 1e4-1e6 viruses per cell

assuming 0.1% of cells are infected, that's 1e16 viruses per infected human.
assuming 1 cold per human per year, that's 1e26 viruses per year.
assuming 0.1% of these go into the atmosphere,that's 1e23.
assuming 0.1% of these are in small enough droplets or clumps
so they won't settle, that's 1e20 rhinoviruses in the atmosphere per year
or 100 cubic meters of rhinoviruses per year if tightly packed.