PMID- 24006442
OWN - NLM
STAT- MEDLINE
DCOM- 20140114
LR  - 20211021
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 87
IP  - 22
DP  - 2013 Nov
TI  - Human herpesvirus 6A infection and immunopathogenesis in humanized Rag2(-)/(-) gammac(-)/(-) 
      mice.
PG  - 12020-8
LID - 10.1128/JVI.01556-13 [doi]
AB  - Although serious human diseases have been correlated with human herpesvirus 6A 
      (HHV-6A) and HHV-6B, the lack of animal models has prevented studies which would 
      more definitively link these viral infections to disease. HHV-6A and HHV-6B have 
      recently been classified as two distinct viruses, and in this study we focused 
      specifically on developing an in vivo model for HHV-6A. Here we show that 
      Rag2(-)/(-)gammac(-)/(-) mice humanized with cord blood-derived human hematopoietic stem 
      cells produce human T cells that express the major HHV-6A receptor, CD46. Both 
      cell-associated and cell-free viral transmission of HHV-6A into the peritoneal 
      cavity resulted in detectable viral DNA in at least one of the samples (blood, 
      bone marrow, etc.) analyzed from nearly all engrafted mice. Organs and cells 
      positive for HHV-6A DNA were the plasma and cellular blood fractions, bone 
      marrow, lymph node, and thymic samples; control mice had undetectable viral DNA. 
      We also noted viral pathogenic effects on certain T cell populations. Specific 
      thymocyte populations, including CD3(-) CD4(+) CD8(-) and CD3(+) CD4(-) cells, were 
      significantly modified in humanized mice infected by cell-associated 
      transmission. In addition, we detected significantly increased proportions of 
      CD4(+) CD8(+) cells in the blood of animals infected by cell-free transmission. These 
      findings provide additional evidence that HHV-6A may play a role in human 
      immunodeficiencies. These results indicate that humanized mice can be used to 
      study HHV-6A in vivo infection and replication as well as aspects of viral 
      pathogenesis.
FAU - Tanner, Anne
AU  - Tanner A
AD  - Department of Microbiology and Molecular Biology, Brigham Young University, 
      Provo, Utah, USA.
FAU - Carlson, Stephanie A
AU  - Carlson SA
FAU - Nukui, Masatoshi
AU  - Nukui M
FAU - Murphy, Eain A
AU  - Murphy EA
FAU - Berges, Bradford K
AU  - Berges BK
LA  - eng
GR  - U54 AI057160/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130904
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (DNA, Viral)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Rag2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Bone Marrow/immunology/pathology/virology
MH  - Cells, Cultured
MH  - DNA, Viral/genetics
MH  - DNA-Binding Proteins/*physiology
MH  - Fetal Blood/immunology/virology
MH  - Flow Cytometry
MH  - Hematopoietic Stem Cells/immunology/*pathology/virology
MH  - Herpesvirus 6, Human/*pathogenicity
MH  - Humans
MH  - Lymph Nodes/immunology/pathology/virology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Roseolovirus Infections/immunology/*transmission/virology
MH  - Spleen/immunology/pathology/virology
MH  - Thymus Gland/immunology/pathology/virology
MH  - *Virus Replication
PMC - PMC3807896
EDAT- 2013/09/06 06:00
MHDA- 2014/01/15 06:00
PMCR- 2014/05/01
CRDT- 2013/09/06 06:00
PHST- 2013/09/06 06:00 [entrez]
PHST- 2013/09/06 06:00 [pubmed]
PHST- 2014/01/15 06:00 [medline]
PHST- 2014/05/01 00:00 [pmc-release]
AID - JVI.01556-13 [pii]
AID - 01556-13 [pii]
AID - 10.1128/JVI.01556-13 [doi]
PST - ppublish
SO  - J Virol. 2013 Nov;87(22):12020-8. doi: 10.1128/JVI.01556-13. Epub 2013 Sep 4.