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Virus found in women with unexplained infertility

A new study has found that a little-known human herpesvirus — HHV-6A — infects the uterine lining in 43% of women with unexplained infertility. It was not found in fertile women.


Conducted by investigators at the University of Ferrara, Italy, the study found the virus generates an immune response in the uterus. The virus activates natural killer immune cells to produce cytokines to attack foreign elements — such as viruses — making it hard for a fertilized egg to lodge.

According to the Centers for Disease Control (CDC), infertility affects approximately 6% of females 15 to 44 years old — which translates into 1.5 million people in the USA. Approximately one quarter of those 1.5 million infertility cases are unexplained. There are few options for treatment.


"This is a surprising and potentially important discovery. If confirmed, the finding may lead to treatments that improve the outcome for a large subset of infertile women."

Anthony Komaroff PhD, Professor, Harvard Medical School, has studied HHV-6.


Human Herpesvirus 6A (HHV-6A) was discovered in 1986 and is one of nine human herpesviruses which include: Epstein Barr, varicella-zoster virus, cytomegalovirus, and herpes simplex types 1 and 2. HHV-6 is actually a set of two closely related herpes viruses — HHV-6A and HHV-6B.

HHV-6B infects nearly all human beings before the age of three with fever, diarrhea, or a rash known as roseola and is spread through exposure to saliva. HHV-6B can cause brain inflammation and disease of other organs in patients with immune deficiencies or on immunosuppressive drugs. Although rare, infection can cause:
(1) febrile seizures — a seizure associated with a high body temperature but without any serious underlying health issue, more commonly in children from 6 months to 5 years

A virus is a small infectious agent that replicates only inside the living cells of another organism.

(2) encephalitis — an acute inflammation of the brain; combined with meningitis, it is known as meningoencephalitisor
(3) intractable seizures in which a seizure fails to come under control with treatment

Little is known about the prevalence of HHV-6A or how it is acquired. One small study found half the healthy adults in that study had very low levels of HHV-6A in their saliva. Since HHV-6A is typically not detectable in blood or saliva, its actual prevalence is unknown.

Currently, there are no FDA-approved drugs for HHV-6A or HHV-6B, but infectious disease specialists commonly use valganciclovir, foscarnet, and cidofovir to treat HHV-6B reactivation in transplant patients. These drugs were developed to treat human herpesvirus-5 (HHV-5) or cytomegalovirus.

More research is needed to confirm these findings and to determine whether antiviral treatment would help women with this uterine infection. Diagnosis of HHV-6A infection of the uterine lining can be made by a biopsy of the uterine lining, a standard procedure done by gynecologists without anesthesia using a small suction device.

Results of the current study are published in the journal PLOS ONE

Abstract
To elucidate the roles of human herpesvirus (HHV)-6 primary unexplained infertile women, a prospective randomized study was conducted on a cohort of primary unexplained infertile women and a cohort of control women, with at least one successful pregnancy. HHV-6 DNA was analyzed and the percentage and immune-phenotype of resident endometrial Natural Killer (NK) cells, as the first line of defense towards viral infections, was evaluated in endometrial biopsies. Cytokine levels in uterine flushing samples were analyzed. HHV-6A DNA was found in 43% of endometrial biopsies from primary unexplained infertile women, but not in control women. On the contrary, HHV-6B DNA was absent in endometrial biopsies, but present in PBMCs of both cohorts. Endometrial NK cells presented a different distribution in infertile women with HHV6-A infection compared with infertile women without HHV6-A infection. Notably, we observed a lower percentage of endometrial specific CD56brightCD16- NK cells. We observed an enhanced HHV-6A-specific endometrial NK cell response in HHV-6A positive infertile women, with a marked increase in the number of endometrial NK cells activating towards HHV-6A infected cells. The analysis of uterine flushing samples showed an increase in IL-10 levels and a decrease of IFN-gamma concentrations in infertile women with HHV6-A infection. Our study indicates, for the first time, that HHV-6A infection might be an important factor in female unexplained infertility development, with a possible role in modifying endometrial NK cells immune profile and ability to sustain a successful pregnancy.

The full article can be found on the PLOS ONE website. Additional information about HHV-6A and the infertility study can be found on the HHV-6 Foundation web site.

ABOUT THE HHV-6 FOUNDATION
The HHV-6 Foundation in a non-profit entity founded to encourage scientific exchange between investigators and to provide pilot grants for promising scientific and clinical research on the under- appreciated viruses HHV-6A and HHV-6B. The Foundation sponsors international conferences and supports scientists and clinicians seeking to clarify the role of the two HHV-6 viruses in disease. Since HHV-6A and HHV-6B can smolder in the brain and other organs without circulating in the peripheral blood or plasma, identifying chronic infection is a challenge.

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Jul 22, 2016   Fetal Timeline   Maternal Timeline   News   News Archive   



Image Credit: HHV-6 Foundation


 


 

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