"Long before it's in the papers"
January 28, 2015


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.”

* * *

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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 could lead to the first effective treatments for the illness. 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 online version of the journal Science on Feb. 12. “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,” 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 causes 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 a span of more than two decades. The study by Palmenberg and colleagues adds 80 genome sequences to the rhinovirus 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 from relatively sick patients. “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.”