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1、Closing the Brief Case:Inherited Chromosomally IntegratedHuman Herpesvirus 6(HHV-6)in the Age of Multiplex HHV-6TestingAlexander L.Greninger,a,bSamia N.Naccache,cPia Pannaraj,dKeith R.Jerome,a,bJennifer Dien Bard,cJeanne W.RudermandaDepartment of Laboratory Medicine,University of Washington,Seattle,
2、Washington,USAbVaccine and Infectious Disease Division,Fred Hutchinson Cancer Research Center,Seattle,Washington,USAcDepartment of Laboratory Medicine,Childrens Hospital Los Angeles,Los Angeles,California,USAdDepartment of Pediatrics,Division of Neonatology,Childrens Hospital Los Angeles,Los Angeles
3、,California,USAKEYWORDSBioFire,HHV-6,ddPCR,ganciclovir,human herpesvirus 6,iciHHV-6,qPCRANSWERS TO SELF-ASSESSMENT QUESTIONS1.Approximately what percentage of the population is iciHHV-6 positive?a.0.03%b.1%c.10%d.50%Answer:b.Depending on the population,approximately 0.5 to 2%of individualscarry HHV-
4、6 integrated into every cell in their body.2.Quantitative estimates of HHV-6 viral load in whole blood are NOT affected bywhich of the following?a.WBC countb.Viral reactivationc.Hemoglobind.iciHHV-6 statusAnswer:c.iciHHV-6 is associated with high viral copy numbers of HHV-6 in allsamples examined.Be
5、cause viral copy number in these patients is associated withthe presence of host DNA and HHV-6 predominantly occurs in pediatric and stemcell transplant patients,preanalytical variables such as white blood cell(WBC)countcan greatly affect measured HHV-6 viral loads.Viral reactivation can also yield
6、5 to 6logs of difference in HHV-6 viral loads measured in the blood.Hemoglobin does notaffect HHV-6 viral load,provided that the internal control amplifies.3.What is the preferred diagnostic test for confirmation of iciHHV-6 status?a.Plasma quantitative viral PCRb.Sequencing of integration sitesc.Qu
7、alitative plasma PCRd.Droplet digital PCRAnswer:d.When iciHHV-6 is suspected,the most common downstream test per-formed is droplet digital PCR(ddPCR).ddPCR enables highly accurate estimation ofviral and host copy number to determine the exact ratio between virus and host.Since almost all iciHHV-6 in
8、dividuals are heterozygote for HHV-6,they will carry 1copy of HHV-6 for every 2 copies of human housekeeping gene.In general,viralloads in whole blood of?5.5 log10are strongly suggestive of iciHHV-6.Citation Greninger AL,Naccache SN,PannarajP,Jerome KR,Dien Bard J,Ruderman JW.2019.Closing the Brief
9、Case:Inheritedchromosomally integrated human herpesvirus6(HHV-6)in the age of multiplex HHV-6testing.J Clin Microbiol 57:e02018-18.https:/doi.org/10.1128/JCM.02018-18.Editor Carey-Ann D.Burnham,WashingtonUniversity School of MedicineCopyright 2019 American Society forMicrobiology.All Rights Reserved
10、.Address correspondence to Alexander L.Greninger,agreninguw.edu.Seehttps:/doi.org/10.1128/JCM.02016-18in thisissue for case presentation and discussion.PublishedTHE BRIEF CASEcrossmOctober 2019Volume 57Issue 10e02018-18jcm.asm.org1Journal of Clinical Microbiology24 September 2019 on July 9,2020 at X
11、ian Jiaotong Universityhttp:/jcm.asm.org/Downloaded from TAKE-HOME POINTSHuman herpesvirus 6B(HHV-6B)is the cause of roseola and is the mostcommon cause of febrile seizures in infants.HHV-6 carries telomeric repeats within its genome and can integrate intosubtelomeric regions of human chromosomes,wh
12、ich may be the viral form oflatency.iciHHV-6 can then be inherited in a Mendelian fashion.Approximately 1%of the human population carries HHV-6 integrated intoevery cell in the human body.These individuals will have high viral loads forHHV-6.Because HHV-6 is now included on an FDA-approved multiplex
13、 panel formeningitis/encephalitis,substantially more patients are being tested for HHV-6.iciHHV-6 testing is typically performed using droplet digital PCR on wholeblood to accurately determine relative copy numbers of viral and host DNA inserum and cell pellet components.The Brief CaseJournal of Clinical MicrobiologyOctober 2019Volume 57Issue 10e02018-18jcm.asm.org2 on July 9,2020 at Xian Jiaotong Universityhttp:/jcm.asm.org/Downloaded from