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研究人员确定了体内可能被COVID-19病毒攻击的特定细胞

研究人员确定了体内可能被COVID-19病毒攻击的特定细胞

研究发现,肺部、鼻腔和肠道中的特定细胞更容易受到感染。

Researchers+at+MIT%3b+the+Ragon+Institute+of+MGH%2c+MIT%2c+and+Harvard%3b+and+the+Broad+Institute+of+MIT+and+Harvard%3b+along+with+colleagues+from+around+the+world+have+identified+specific+types+of+cells+that+appear+to+be+targets+of+the+coronavirus+that+is+causing+the+Covid-19+pandemic.%0aUsing+existing+data+on+the+RNA+found+in+different+types+of+cells%2c+the+researchers+were+able+to+search+for+cells+that+express+the+two+proteins+that+help+the+SARS-CoV-19+virus+enter+human+cells.+They+found+subsets+of+cells+in+the+lung%2c+the+nasal+passages%2c+and+the+intestine+that+express+RNA+for+both+of+these+proteins+much+more+than+other+cells.%0aThe+researchers+hope+that+their+findings+will+help+guide+scientists+who+are+working+on+developing+new+drug+treatments+or+testing+existing+drugs+that+could+be+repurposed+for+treating+Covid-19.%0a%26ldquo%3bOur+goal+is+to+get+information+out+to+the+community+and+to+share+data+as+soon+as+is+humanly+possible%2c+so+that+we+can+help+accelerate+ongoing+efforts+in+the+scientific+and+medical+communities%2c%26rdquo%3b+says+Alex+K.+Shalek%2c+the+Pfizer-Laubach+Career+Development+Associate+Professor+of+Chemistry%2c+a+core+member+of+MIT%26rsquo%3bs+Institute+for+Medical+Engineering+and+Science+(IMES)%2c+an+extramural+member+of+the+Koch+Institute+for+Integrative+Cancer+Research%2c+an+associate+member+of+the+Ragon+Institute%2c+and+an+institute+member+at+the+Broad+Institute.%0aShalek+and+Jose+Ordovas-Montanes%2c+a+former+MIT+postdoc+who+now+runs+his+own+lab+at+Boston+Children%26rsquo%3bs+Hospital%2c+are+the+senior+authors+of+the+study%2c+which+appears+today+in+Cell.+The+paper%26rsquo%3bs+lead+authors+are+MIT+graduate+students+Carly+Ziegler%2c+Samuel+Allon%2c+and+Sarah+Nyquist%3b+and+Ian+Mbano%2c+a+researcher+at+the+Africa+Health+Research+Institute+in+Durban%2c+South+Africa.%0aDigging+into+data%0aNot+long+after+the+SARS-CoV-2+outbreak+began%2c+scientists+discovered+that+the+viral+%26ldquo%3bspike%26rdquo%3b+protein+binds+to+a+receptor+on+human+cells+known+as+angiotensin-converting+enzyme+2+(ACE2).+Another+human+protein%2c+an+enzyme+called+TMPRSS2%2c+helps+to+activate+the+coronavirus+spike+protein%2c+to+allow+for+cell+entry.+The+combined+binding+and+activation+allows+the+virus+to+get+into+host+cells.%0a%26ldquo%3bAs+soon+as+we+realized+that+the+role+of+these+proteins+had+been+biochemically+confirmed%2c+we+started+looking+to+see+where+those+genes+were+in+our+existing+datasets%2c%26rdquo%3b+Ordovas-Montanes+says.+%26ldquo%3bWe+were+really+in+a+good+position+to+start+to+investigate+which+are+the+cells+that+this+virus+might+actually+target.%26rdquo%3b%0aShalek%26rsquo%3bs+lab%2c+and+many+other+labs+around+the+world%2c+have+performed+large-scale+studies+of+tens+of+thousands+of+human%2c+nonhuman+primate%2c+and+mouse+cells%2c+in+which+they+use+single-cell+RNA+sequencing+technology+to+determine+which+genes+are+turned+on+in+a+given+cell+type.+Since+last+year%2c+Nyquist+has+been+building+a+database+with+partners+at+the+Broad+Institute+to+store+a+huge+collection+of+these+datasets+in+one+place%2c+allowing+researchers+to+study+potential+roles+for+particular+cells+in+a+variety+of+infectious+diseases.%0aMuch+of+the+data+came+from+labs+that+belong+to+the+Human+Cell+Atlas+project%2c+whose+goal+is+to+catalog+the+distinctive+patterns+of+gene+activity+for+every+cell+type+in+the+human+body.+The+datasets+that+the+MIT+team+used+for+this+study+included+hundreds+of+cell+types+from+the+lungs%2c+nasal+passages%2c+and+intestine.+The+researchers+chose+those+organs+for+the+Covid-19+study+because+previous+evidence+had+indicated+that+the+virus+can+infect+each+of+them.+They+then+compared+their+results+to+cell+types+from+unaffected+organs.%0a%26ldquo%3bBecause+we+have+this+incredible+repository+of+information%2c+we+were+able+to+begin+to+look+at+what+would+be+likely+target+cells+for+infection%2c%26rdquo%3b+Shalek+says.+%26ldquo%3bEven+though+these+datasets+weren%26rsquo%3bt+designed+specifically+to+study+Covid%2c+it%26rsquo%3bs+hopefully+given+us+a+jump+start+on+identifying+some+of+the+things+that+might+be+relevant+there.%26rdquo%3b%0aIn+the+nasal+passages%2c+the+researchers+found+that+goblet+secretory+cells%2c+which+produce+mucus%2c+express+RNAs+for+both+of+the+proteins+that+SARS-CoV-2+uses+to+infect+cells.+In+the+lungs%2c+they+found+the+RNAs+for+these+proteins+mainly+in+cells+called+type+II+pneumocytes.+These+cells+line+the+alveoli+(air+sacs)+of+the+lungs+and+are+responsible+for+keeping+them+open.%0aIn+the+intestine%2c+they+found+that+cells+called+absorptive+enterocytes%2c+which+are+responsible+for+the+absorption+of+some+nutrients%2c+express+the+RNAs+for+these+two+proteins+more+than+any+other+intestinal+cell+type.%0a%26ldquo%3bThis+may+not+be+the+full+story%2c+but+it+definitely+paints+a+much+more+precise+picture+than+where+the+field+stood+before%2c%26rdquo%3b+Ordovas-Montanes+says.+%26ldquo%3bNow+we+can+say+with+some+level+of+confidence+that+these+receptors+are+expressed+on+these+specific+cells+in+these+tissues.%26rdquo%3b%0aFighting+infection%0aIn+their+data%2c+the+researchers+also+saw+a+surprising+phenomenon+%26mdash%3b+expression+of+the+ACE2+gene+appeared+to+be+correlated+with+activation+of+genes+that+are+known+to+be+turned+on+by+interferon%2c+a+protein+that+the+body+produces+in+response+to+viral+infection.+To+explore+this+further%2c+the+researchers+performed+new+experiments+in+which+they+treated+cells+that+line+the+airway+with+interferon%2c+and+they+discovered+that+the+treatment+did+indeed+turn+on+the+ACE2+gene.%0aInterferon+helps+to+fight+off+infection+by+interfering+with+viral+replication+and+helping+to+activate+immune+cells.+It+also+turns+on+a+distinctive+set+of+genes+that+help+cells+fight+off+infection.+Previous+studies+have+suggested+that+ACE2+plays+a+role+in+helping+lung+cells+to+tolerate+damage%2c+but+this+is+the+first+time+that+ACE2+has+been+connected+with+the+interferon+response.%0aThe+finding+suggests+that+coronaviruses+may+have+evolved+to+take+advantage+of+host+cells%26rsquo%3b+natural+defenses%2c+hijacking+some+proteins+for+their+own+use.%0a%26ldquo%3bThis+isn%26rsquo%3bt+the+only+example+of+that%2c%26rdquo%3b+Ordovas-Montanes+says.+%26ldquo%3bThere+are+other+examples+of+coronaviruses+and+other+viruses+that+actually+target+interferon-stimulated+genes+as+ways+of+getting+into+cells.+In+a+way%2c+it%26rsquo%3bs+the+most+reliable+response+of+the+host.%26rdquo%3b%0aBecause+interferon+has+so+many+beneficial+effects+against+viral+infection%2c+it+is+sometimes+used+to+treat+infections+such+as+hepatitis+B+and+hepatitis+C.+The+findings+of+the+MIT+team+suggest+that+interferon%26rsquo%3bs+potential+role+in+fighting+Covid-19+may+be+complex.+On+one+hand%2c+it+can+stimulate+genes+that+fight+off+infection+or+help+cells+survive+damage%2c+but+on+the+other+hand%2c+it+may+provide+extra+targets+that+help+the+virus+infect+more+cells.%0a%26ldquo%3bIt%26rsquo%3bs+hard+to+make+any+broad+conclusions+about+the+role+of+interferon+against+this+virus.+The+only+way+we%26rsquo%3bll+begin+to+understand+that+is+through+carefully+controlled+clinical+trials%2c%26rdquo%3b+Shalek+says.+%26ldquo%3bWhat+we+are+trying+to+do+is+put+information+out+there%2c+because+there+are+so+many+rapid+clinical+responses+that+people+are+making.+We%26rsquo%3bre+trying+to+make+them+aware+of+things+that+might+be+relevant.%26rdquo%3b%0aShalek+now+hopes+to+work+with+collaborators+to+profile+tissue+models+that+incorporate+the+cells+identified+in+this+study.+Such+models+could+be+used+to+test+existing+antiviral+drugs+and+predict+how+they+might+affect+SARS-CoV-2+infection.%0aThe+MIT+team+and+their+collaborators+have+made+all+the+data+they+used+in+this+study+available+to+other+labs+who+want+to+use+it.+Much+of+the+data+used+in+this+study+was+generated+in+collaboration+with+researchers+around+the+world%2c+who+were+very+willing+to+share+it%2c+Shalek+says.%0a%26ldquo%3bThere%26rsquo%3bs+been+an+incredible+outpouring+of+information+from+the+scientific+community+with+a+number+of+different+parties+interested+in+contributing+to+the+battle+against+Covid+in+any+way+possible%2c%26rdquo%3b+he+says.+%26ldquo%3bIt%26rsquo%3bs+been+incredible+to+see+a+large+number+of+labs+from+around+the+world+come+together+to+try+and+collaboratively+tackle+this.%26rdquo%3b%0aThe+research+was+funded+by+the+Searle+Scholars+Program%2c+the+Beckman+Young+Investigator+Program%2c+the+Pew-Stewart+Scholars+Program+for+Cancer+Research%2c+a+Sloan+Fellowship+in+Chemistry%2c+the+National+Institutes+of+Health%2c+the+Aeras+Foundation%2c+the+Bill+and+Melinda+Gates+Foundation%2c+the+Richard+and+Susan+Smith+Family+Foundation%2c+the+National+Institute+of+General+Medical+Sciences%2c+the+UMass+Center+for+Clinical+and+Translational+Science+Project+Pilot+Program%2c+the+MIT+Stem+Cell+Initiative%2c%26nbsp%3bFondation+MIT%2c+and+the+Office+of+the+Assistant+Secretary+of+Defense+for+Health+Affairs.

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