Human herpesvirus 6A infection and immunopathogenesis in humanized Rag2⁻/⁻ γc⁻/⁻ mice.
http://www.ncbi.nlm.nih.gov/pubmed/24006442
Abstract
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⁻/⁻γc⁻/⁻ 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.
