Ebola evolved into dead­lier epi­demic

Lesotho Times - - Africa -

NEW YORK — The Ebola epi­demic that tore through West Africa in 2014 claimed 11 310 lives, far more than any previous out­break. A com­bi­na­tion of fac­tors contributed to its sav­agery, among them a mo­bile pop­u­la­tion, crum­bling pub­lic health sys­tems, of­fi­cial ne­glect and haz­ardous burial prac­tices.

But new re­search sug­gests another im­pe­tus: The virus may have evolved a new weapon against its hu­man hosts.

In stud­ies pub­lished last Thurs­day in the jour­nal Cell, two teams of sci­en­tists re­port that a ge­netic mu­ta­tion may have made Ebola more deadly by im­prov­ing the virus’s abil­ity to en­ter hu­man cells.

The re­searchers do not yet un­der­stand ex­actly how it works, but sev­eral lines of ev­i­dence sug­gest it helped ex­pand the scope of the epi­demic. One alarming find­ing: Pa­tients in­fected with the mu­tated ver­sion of Ebola were sig­nif­i­cantly more likely to die.

“It’s hard to es­cape the con­clu­sion that it’s an adap­ta­tion to the hu­man host,” said Dr. Jeremy Luban, a vi­rol­o­gist at the Univer­sity of Mas­sachusetts Med­i­cal School and an au­thor of one of the new stud­ies.

Nor­mally, Ebola cir­cu­lates among an­i­mal hosts, prob­a­bly African bats. Sci­en­tists sus­pect that the West African epi­demic be­gan when a bat in­fected a boy in a vil­lage in Guinea in December 2013.

As re­ports of the out­break sur­faced, Dr Pardis Sa­beti, a com­pu­ta­tional bi­ol­o­gist at Har­vard, and her col­leagues started a col­lab­o­ra­tion with doc­tors in Sierra Leone. The re­searchers quickly se­quenced the genomes of 99 Ebola viruses iso­lated from 78 pa­tients there.

Their anal­y­sis showed that Ebola was mov­ing quickly from one vic­tim to the next, and that the virus was gain­ing new mu­ta­tions along the way. One wor­ry­ing pos­si­bil­ity was that those mu­ta­tions some­how sped up Ebola’s repli­ca­tion.

But it was also pos­si­ble these changes didn’t mean any­thing at all. “We know that viruses mu­tate,” Dr. Sa­beti said. “There was noth­ing rev­e­la­tory in that.”

Each of Ebola’s seven genes en­codes a pro­tein. Even if a gene is al­tered with a mu­ta­tion, it may end up mak­ing pre­cisely the same pro­tein as be­fore, or one that works ex­actly the same way.

Last year com­puter sim­u­la­tions by Dr. Si­mon C. Lovell, an evo­lu­tion­ary bi­ol­o­gist at the Univer­sity of Manch­ester, and his col­leagues did not find any im­por­tant dif­fer­ence in Ebola’s pro­teins caused by the new mu­ta­tions. But that work was based only on what sci­en­tists knew about the molec­u­lar bi­ol­ogy of Ebola at the time.

There was still a lot left to learn, it turned out. Dr. Sa­beti and her col­leagues went on to an­a­lyze 1,489 Ebola genomes, trac­ing the virus’s de­vel­op­ment over the course of the epi­demic in an evo­lu­tion­ary tree.

The tree showed that one mu­ta­tion arose at a cru­cial point in the out­break. Known as GPA82V, it was first ob­served in vi­ral sam­ples col­lected from a pa­tient in Guinea on March 31, 2014.

Ebola viruses car­ry­ing GPA82V ex­ploded across all three coun­tries. The orig­i­nal ver­sion of the virus, by con­trast, sput­tered on at low lev­els in Guinea be­fore dis­ap­pear­ing in a cou­ple of months.

The GPA82V mu­ta­tion al­ters the gene that di­rects pro­duc­tion of Ebola’s sur­face pro­teins, called gly­co­pro­teins. The tips of these pro­teins con­tact hu­man host cells, open­ing a pas­sage­way by which the virus en- ters.

To judge the ef­fects of the mu­ta­tion, Dr Luban cre­ated a form of HIV stud­ded with Ebola’s sur­face pro­teins and ob­served as these hy­brid viruses in­fected hu­man cells. One set of hy­brid viruses con­tained the GPA82V mu­ta­tion; the other con­tained the orig­i­nal ver­sion of the Ebola gene.

The mu­ta­tion, the sci­en­tists found, made the viruses much more suc­cess­ful at at­tack­ing hu­man cells and those of other pri­mates. Com­pared with the older gene, the mu­tated form in­fected four times as many pri­mate cells.

But the mu­ta­tion did not help the hy­brid viruses in­fect the cells of other species, such as cats and dogs.

In a par­al­lel study also pub­lished on Thurs­day, Jonathan K. Ball, a vi­rol­o­gist at the Univer­sity of Not­ting­ham, and his col­leagues an­a­lyzed 1,610 Ebola genomes and ar­rived at the same con­clu­sion as Dr. Sa­beti: The GPA82V mu­ta­tion arose early in the West African epi­demic and spread like wild­fire.

Dr. Ball’s team also cre­ated hy­brid viruses — in­stead of HIV, they used mouse viruses — and found that GPA82V made them twice as in­fec­tious to hu­man cells.

The sci­en­tists also tried in­fect­ing cells from fruit bats, in­clud­ing an African species thought to be Ebola’s nat­u­ral host. The mu­ta­tion ac­tu­ally made the viruses worse at in­fect­ing the bat cells.

Dr. Lovell said he and his col­leagues had com­pleted a study of their own, now un­der re­view at a jour­nal that pro­duced sim­i­lar find­ings. As a re­sult, he is no longer a skep­tic.

“Now it seems there is a change,” he said of the Ebola virus. “What we don’t know yet is the ef­fect on peo­ple.”

Dr. Sa­beti and her col­leagues have dis­cov­ered some fright­en­ing clues in pa­tient med­i­cal records. Among 194 cases, they found, peo­ple in­fected with mu­tated Ebola were sig­nif­i­cantly more likely to die than those with the older strain.

Col­lec­tively, Dr. Luban said, the ev­i­dence points strongly to the con­clu­sion that Ebola’s mu­ta­tion helped it spread more ef­fec­tively in peo­ple.

“It looks like a duck, and so I think it prob­a­bly is a duck,” he said.

It is not clear what role the mu­ta­tion played in West Africa’s epi­demic. Per­haps it was only mi­nor, com­pared with ge­og­ra­phy and the poor state of re­gion’s pub­lic health sys­tems, Dr. Ball said.

But the fact that Ebola did gain at least one ad­van­tage that made it bet­ter at in­fect­ing hu­man cells wor­ries him any­way. We will al­most cer­tainly face another out­break.

“You will see that virus try­ing to adapt to its new host,” he said. “And the longer you let that spillover take place, the more chance it has to be­come bet­ter adapted.”

— NY Times

A burial in liberia for an Ebola vic­tim in oc­to­ber 2014. The epi­demic claimed 11,310 lives.

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