快速传播的变异帮助普通流感亚型逃避免疫反应

- 编辑:大众自然网 -

快速传播的变异帮助普通流感亚型逃避免疫反应

这一发现强调了流感疫苗需要针对病毒的多个部位。

Strains+of+a+common+subtype+of+influenza+virus%2c+H3N2%2c+have+almost+universally+acquired+a+mutation+that+effectively+blocks+antibodies+from+binding+to+a+key+viral+protein%2c+according+to+a+study+from+researchers+at+Johns+Hopkins+Bloomberg+School+of+Public+Health.%0aThe+results+have+implications+for+flu+vaccine+design%2c+according+to+the+researchers.+Current+flu+vaccines%2c+which+are+%26ldquo%3bseasonal+vaccines%26rdquo%3b+designed+to+protect+against+recently+circulating+flu+strains%2c+induce+antibody+responses+mostly+against+a+different+viral+protein+called+hemagglutinin.%0aThe+new+mutation%2c+described+in+the+study+published+online+June+29+in+PLOS+Pathogens%2c+was+first+detected+in+the+2014-2015+flu+season+in+some+H3N2+flu+strains%2c+and+evidently+is+so+good+at+boosting+flu%26rsquo%3bs+ability+to+spread+that+it+is+now+present+in+virtually+all+circulating+H3N2+strains.+Recent+flu+seasons%2c+in+which+H3N2+strains+have+featured+prominently%2c+have+been+relatively+severe+compared+to+historical+averages.%0aThe+mutation+alters+a+viral+protein+called+neuraminidase%2c+and+the+researchers+found+in+their+study+that+this+alteration+paradoxically+reduces+the+ability+of+flu+virus+to+replicate+in+a+type+of+human+nasal+cell+that+it+normally+infects.+However%2c+the+researchers+also+found+evidence+that+the+mutation+more+than+compensates+for+this+deficit+by+setting+up+a+physical+barrier+that+hinders+antibodies+from+binding+to+neuraminidase.%0a%26ldquo%3bThese+findings+tell+us+that+flu+vaccines+focusing+on+the+hemagglutinin+protein+are+leaving+the+virus+openings+to+evolve+and+evade+other+types+of+immunity%2c%26rdquo%3b+says+study+senior+author+Andrew+Pekosz%2c+PhD%2c+professor+and+vice+chair+of+the+Department+of+Molecular+Microbiology+and+Immunology+at+the+Bloomberg+School.%0aEvery+year%2c+influenza+viruses+sicken+millions+of+people+around+the+world%2c+killing+several+hundred+thousands.+The+diversity+of+flu+strains+and+their+ability+to+mutate+rapidly+%26mdash%3b+two+strains+infecting+the+same+host+can+even+swap+genes+%26mdash%3b+have+made+flu+viruses+an+especially+difficult+target+for+vaccine+designers.+Although+scientists+are+working+towards+a+universal+vaccine+that+will+protect+long-term+against+most+flu+variants%2c+current+flu+vaccines+are+designed+to+protect+against+only+a+short+list+of+recently+circulating+strains.+Any+mutation+that+occurs+in+these+circulating+strains+and+appears+to+improve+their+ability+to+spread+is+naturally+of+interest+to+flu+virologists.%0aThe+goal+of+the+study+was+to+understand+better+the+workings+of+the+new+H3N2+mutation.+Scientists+have+known+that+it+alters+the+flu+virus%26rsquo%3bs+neuraminidase+protein+in+a+way+that+provides+an+attachment+point%2c+close+to+neuraminidase%26rsquo%3bs+active+site%2c+for+a+sugar-like+molecule+called+a+glycan.+But+how+the+presence+of+a+glycan+at+that+location+on+the+neuraminidase+protein+improves+the+virus%26rsquo%3bs+ability+to+infect+hosts+and+spread+hasn%26rsquo%3bt+been+clear.%0aPekosz+and+first+author+Harrison+Powell%2c+PhD%2c+a+graduate+student+in+his+laboratory+at+the+time+of+the+study%2c+compared+the+growth%2c+in+laboratory+cells%2c+of+typical+H3N2+strains+that+have+the+glycan-attachment+mutation+to+the+growth+of+the+same+flu+strains+without+the+mutation.+They+found+that+the+mutant+versions+grew+markedly+more+slowly+in+human+cells+from+the+lining+of+the+nasal+passages+%26mdash%3b+a+cell+type+that+a+flu+virus+would+initially+infect.%0aThe+researchers+found+the+likely+reason+for+this+slower+growth%3a+the+glycan-attracting+mutation+hinders+the+activity+of+neuraminidase.+The+protein+is+known+to+serve+as+a+crucial+flu+enzyme+whose+functions+include+clearing+a+path+for+the+virus+through+airway+mucus%2c+and+enhancing+the+release+of+new+virus+particles+from+infected+cells.%0aIt+wasn%26rsquo%3bt+entirely+unexpected+that+the+addition+of+a+moderately+bulky+glycan+molecule+near+the+enzyme%26rsquo%3bs+active+site+would+have+this+effect.+But+it+left+unexplained+how+that+would+benefit+the+virus.%0aThe+scientists+solved+the+mystery+by+showing+that+the+glycan+blocks+antibodies+that+would+otherwise+bind+to+or+near+the+active+site+of+the+neuraminidase+enzyme.%0aNeuraminidase%2c+especially+its+active+site%2c+is+considered+one+of+the+most+important+targets+for+the+immune+response+to+a+flu+infection.+It+is+also+the+target+of+flu+drugs+such+as+Tamiflu+(oseltamivir).+Thus+it+makes+sense+that+a+mutation+protecting+that+target+confers+a+net+benefit+to+the+virus%2c+even+if+it+means+that+the+neuraminidase+enzyme+itself+works+less+efficiently.%0aThe+finding+highlights+the+potential+for+flu+viruses+to+evade+therapies%2c+seasonal+vaccines%2c+and+the+ordinary+immune+response%2c+Pekosz+says%2c+and+points+to+the+need+for+targeting+multiple+sites+on+the+virus+to+reduce+the+chance+that+single+mutations+can+confer+such+resistance.%0aThe+researchers+have+been+following+up+their+findings+with+studies+of+how+the+new+mutation+affects+the+severity+of+flu%2c+how+it+has+spread+so+rapidly+among+H3N2+strains%2c+and+how+these+altered+flu+strains+have+adapted+with+further+mutations.%0a%26ldquo%3bNeuraminidase+antigenic+drift+of+influenza+A+virus+H3N2+clade+3c.2a+viruses+alters+virus+replication%2c+enzymatic+activity+and+inhibitory+antibody+binding%26rdquo%3b+was+written+by+Harrison+Powell+and+Andrew+Pekosz.%0a%23%23%23%0aReference%3a+%26ldquo%3bNeuraminidase+antigenic+drift+of+H3N2+clade+3c.2a+viruses+alters+virus+replication%2c+enzymatic+activity+and+inhibitory+antibody+binding%26rdquo%3b+by+Harrison+Powell+and+Andrew+Pekosz%2c+29+June+2020%2c+PLOS+Pathogens.%0aDOI%3a+10.1371%2fjournal.ppat.1008411%0aThe+study+was+supported+by+the+National+Institute+of+Allergy+and+Infectious+Diseases+(CEIRS+HHSN272201400007C)+and+the+National+Institutes+of+Health+(T32+AI007417).

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