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ciHHV-6B activation and fetal transmission in response to high dose progesterone?

In All, ciHHV-6, Endocrine Conditions, Infertility & Miscarriage by Kristin Loomis

A pregnant ciHHV-6B woman with a history of miscarriages was given weekly doses of high dose progesterone. When her baby was born with dilated cardiomyopathy and died shortly after birth, an autopsy revealed signs of active HHV-6 infection. The investigators suspected one of the drugs she took during pregnancy might have activated her chromosomally integrated HHV-6. They used her cells to perform cell cultures and found that progesterone, like hydrocortisone, can activate integrated ciHHV-6 in vitro. The authors conclude that there is an urgent need for further study as high dose progesterone may be contraindicated for ciHHV-6 women during pregnancy.

Active HHV-6 virus can be shed by ciHHV-6 individuals who are immunosuppressed. Shedding can also occur in pregnant ciHHV-6 women, and active infection can be passed from the mother to the fetus transplacentally (Gravel 2013). Certain drugs including HDAC inhibitors and hydrocortisone can activate the integrated virus (Arbuckle 2010). This is the first report of progesterone activating integrated HHV-6. The investigators identified HHV-6 by in situ hybridization and by using immunohistochemistry, found “late” proteins (a sign of active HHV-6 replication) in the heart and other tissues.

Dr. Bibhuti Das of Children’s Medical Center, University of Texas

Dr. Bibhuti Das of Children’s Medical Center, University of Texas

Cardiologist Bibhuti Das, MD, of the University of Texas Southwestern Medical Center in Dallas, speculates that the fetal HHV-6 infection occurred during the second trimester, as suggested by the extensive scar tissue or fibrosis that resulted in dilated cardiomyopathy at birth.

Of interest, the mother had a previous pregnancy in which she lost twin fetuses in the second trimester. Investigators stained stored paraffin block placental tissues from that pregnancy and found evidence of active HHV-6B infection in those tissues as well. The authors noted that in a subsequent pregnancy, the mother declined high dose progesterone and delivered a healthy baby. Placental tissues from the final, successful pregnancy tested negative for active infection.

The immunohistochemistry and invitro testing was done by Bhupesh Prusty, PhD, from the University of Würzburg in Germany, who cultured ciHHV-6 peripheral blood mononuclear cells for two weeks in the presence of progesterone.

High dose progesterone is a common treatment for women at risk for miscarriage.

For more information, read the full paper in the Journal of Heart & Lung Transplantation.