Could treatment of HHV-6A co-infections slow AIDS progression?
A group led by Dr. Bradford Berges from Brigham Young University infected humanized mice with HHV-6A and demonstrated evidence for both acute and persistent infection, indicating a new model to study HHV-6A infection in vivo, according to a new report published in Journal of Virology. Infection was accompanied by depletion of specific thymocyte populations as well as detection of elevated levels of CD4+CD8+ T cells in blood. Human herpesvirus 6A (HHV-6A) infects helper T cells and has been suggested to act as a co-factor in AIDS progression. These findings provide additional evidence that HHV-6A infection has a significant impact on human T cell populations in vivo.
The group from Brigham Young University plans to use this model to study the effects of HIV and HHV-6A co-infection in mice. The model also has the potential to be useful in studying the role of HHV-6A as a trigger of MS and the possible role of HHV-6A in CFS.
“This is exciting because it suggests that HHV-6A therapy may be able to slow down AIDS progression”, said Dr. Berges. “It is clear that AIDS is a complicated disease with a variety of contributing factors, such as host genetic and infectious agents. This research suggests a new way to treat HIV/AIDS by targeting a herpesvirus that is attacking the same types of immune cells as HIV.”
An earlier study by NIAID investigator Paolo Lusso showed that macaques co-infected with Simian Immodeficiency Virus (SIV) and HHV-6A had more rapid CD4 depletion and AIDS progression than those infected with SIV alone. A CD46 transgenic mouse model has also been developed for HHV-6A, by a group in France led by Branka Horvat at INSERM. HHV-6A infected mice demonstrated motor weakness, facial palsy, sensory problems and brain lesions. HHV-6B cannot infect CD46 transgenic mice; CD134 has recently been determined to be the receptor for HHV-6B. A recent study by the Jacobson lab at NINDS demonstrated that common marmosets infected with HHV-6A exhibit neurological symptoms.
In this study, the group showed 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 in 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 whereas control mice had undetectable viral DNA. Viral pathogenic effects on certain T cell populations were also observed. Specific thymocyte populations were significantly modified in cell-associated infected humanized mice, including CD3-CD4+CD8- and CD3+CD4- cells. In addition, they detected significantly increased proportions of CD4+CD8+ cells in the blood of cell-free infected animals. These findings provide additional evidence that HHV-6A may play a role in human immunodeficiencies and that humanized mice can be used to study in vivo infection and replication of HHV-6A.
The study was funded by a pilot grant from the HHV-6 Foundation.
For more information, read the full paper.