Human Herpesviruses 6A and 6B in Reproductive Diseases.

Anthony L. Komaroff,Roberta Rizzo,Jeffrey L. Ecker

doi:10.3389/fimmu.2021.648945

Abstract

Human herpesviruses 6A (HHV-6A) and human herpesvirus 6B (HHV-6B)—collectively, HHV-6A/B—are recently-discovered but ancient human viruses. The vast majority of people acquire one or both viruses, typically very early in life, producing an ineradicable lifelong infection. The viruses have been linked to several neurological, pulmonary and hematological diseases. In early human history, the viruses on multiple occasions infected a germ cell, and integrated their DNA into a human chromosome. As a result, about 1% of humans are born with the full viral genome present in every cell, with uncertain consequences for health. HHV-6A may play a role in 43% of cases of primary unexplained infertility. Both the inherited and acquired viruses may occasionally trigger several of the factors that are important in the pathogenesis of preeclampsia. Transplacental infection occurs in 1-2% of pregnancies, with some evidence suggesting adverse health consequences for the child. While emerging knowledge about these viruses in reproductive diseases is not sufficient to suggest any changes in current practice, we write this review to indicate the need for further research that could prove practice-changing.

Highlights

Human herpesvirus-6A (HHV-6A) and human herpesvirus-6B (HHV-6B)—collectively, HHV-6A/ B—are ancient human viruses that were discovered only about 30 years ago [1, 2]
The analysis revealed only two viruses to be correlated with PE: HHV-6A/B
Defective Angiogenesis An excess of antiangiogenic forces relative to angiogenic forces is seen in PE. This is reflected by increased plasma levels of soluble endoglin plus an increased ratio of soluble tms-like tyrosine kinase 1/placental growth factor (PIGF), which are strongly predictive of PE [68,69,70]

Summary

INTRODUCTION

Human herpesvirus-6A (HHV-6A) and human herpesvirus-6B (HHV-6B)—collectively, HHV-6A/ B—are ancient human viruses that were discovered only about 30 years ago [1, 2]. If the viruses play a role in these conditions, it may be due to their ability to infect endometrial epithelial cells, placental cells, natural killer (NK) cells and the endothelial cells of myometrial spiral arteries—and due to the immune response to infection. In a non-pregnant woman, when endometrial epithelial cells are infected by HHV-6A, the NK cytotoxic attack is severe, leading to the production of proinflammatory cytokines that inhibit implantation [47]. HHV-6A (but not HHV-6B) DNA was found in the endometrial epithelial cells of 43% of women with primary unexplained infertility vs none of the fertile controls, a highly significant difference (P

Summary

Findings

CONCLUSION