HHV-6 in Infertility
Human herpesvirus 6 (HHV-6) is suspected to be involved in several types of gestational complications, including spontaneous abortions, gestational hypertension and preterm birth. According to a study published in PLOS Pathogens (Marci R, et al, 2016) HHV-6A is found in 43% of women with unexplained infertility. The ability of HHV-6 to disrupt the uterine environment and fetal development may result in infertility and pregnancy loss. The virus can only be detected in uterine epithelial cells and not in blood samples using traditional HHV-6 testing methods.
Coppe Laboratories’ Immunohistochemical (IHC) staining for HHV-6 has proven to be the most sensitive method for detection of active viral replication in tissue samples. With the growing evidence of an association between HHV- 6 and infertility, we recommend testing endometrial tissue from patients presenting with unexplained infertility, repeat failure to implant and multiple miscarriages.
- Marci R et al. (2016) Presence of HHV-6A in Endometrial Epithelial Cells from Women with Primary Unexplained Infertility. PLoS ONE 11(7): e0158304.
- Eliassen et al. Med Hypotheses. 2017 May;102:41-47.
Arthropod-borne Disease in Pregnancy
During the 2015 outbreak of Zika virus infections in Brazil it was discovered that Zika virus infection during pregnancy places the fetus at risk of developing birth defects. Recent studies have shown that Zika may not be the only arthropod-borne virus that can cause abnormalities in babies born to infected mothers. Other closely-related viruses, primarily mosquito-borne West Nile virus and tick-borne Powassan virus, demonstrate the ability to cause a range of mild to severe brain damage in the fetuses of mice infected during pregnancy. Powassan and West Nile virus were also found to infect and replicate readily in human maternal and fetal placental tissue samples.
Coppe Laboratories offers antibody testing for West Nile virus and the only commercially-available array of tests for Powassan. The CDC recommends screening pregnant women who suspect they may have had exposure to Zika virus at each prenatal visit. Coppe Laboratories is the only commercial lab that offers prenatal screening tests for West Nile and Powassan virus in the US.
Another recent paper examined two case studies of congenital Babesia infection that prompted new questions about tick-borne infections in pregnancy. In both cases, the mothers were diagnosed with Lyme disease during their second trimester of pregnancy. Both were treated with antibiotics and recovered. Their babies were born full term, and neither had any evidence of Lyme, consistent with previous studies that show Lyme disease can be successfully treated during pregnancy without fetal complications. Unfortunately, both babies contracted congenital Babesia infections, forcing these weeks old infants into 5-10 day hospital stays in order to receive necessary treatment. In retrospect it was discovered that both mothers had acquired subclinical Babesia infections during pregnancy which were not diagnosed or treated. Any woman with a suspected tick exposure during pregnancy should be tested for Lyme disease, Babesia and Powassan to avoid fetal developmental abnormalities and complications for newborns.
- D.J. Platt et al., “Zika virus–related neurotropic flaviviruses infect human placental explants and cause fetal demise in mice,” Sci Transl Med, doi:10.1126/scitranslmed.aao7090, 2018.
- Saetre et al. Congenital Babesiosis After Maternal Infection With Borrelia burgdorferi and Babesia microti. Journal of the Pediatric Infectious Diseases Society, pix074,https://doi.org/10.1093/jpids/pix074.
Transplant Testing for Human Herpesviruses
Coppe Laboratories’ scientists have a long history in the study and diagnosis of viral infections in transplant patients. Drs. Knox and Carrigan were among the first scientists to correlate symptoms of pneumonitis, encephalitis, and graft failure in bone marrow transplant recipients with reactivation of HHV-6.
Until now, testing for HHV-6 has lacked the specificity for differentiating between latent and active infection. Coppe Laboratories performs reverse transcription polymerase chain reaction (RT-PCR) which is a a sensitive and powerful tool for analyzing active, replicating virus.
Coppe Laboratories is currently the only reference laboratory performing comprehensive testing for chromosomally integrated HHV-6 (ciHHV-6) on blood, hair follicle and nail clippings.
We are also currently the only reference laboratory providing immunohistochemical staining of tissues to denote active HHV-6 infection.
People with some chronic illnesses (including tick-borne illnesses) are at high risk of suffering additional viral and bacterial infections because of their immune system dysfunction.
CMV, EBV, HHV-6A and HHV-6B are all members of the human herpesvirus family. HHV-6 infects nearly all people before the age of 2 and in children it causes a disease called roseola. HHV-6 and the other herpesviruses establish life-long infection, and while they are usually maintained in a dormant or “latent” state, they can become active again especially during times of immune dysregulation. The symptoms of HHV-6 related illness closely mimic those of Lyme disease. For patients experiencing long-lasting symptoms, testing for these viruses is warranted. Because nearly every person has latent HHV-6, it is imperative that testing is done to establish if the virus is activated. Testing performed at most laboratories cannot distinguish between the latent virus and active HHV-6.
Coppe Laboratories performs testing that determines active infection for HHV-6 and we are the only reference laboratory to provide that testing. For more information please review the testing for HHV-6.
Chromosomally Integrated HHV-6
HHV-6 exists in a chromosomally integrated form (ciHHV-6) whereby the viral DNA resides in every somatic and germ cell in the body. Patients with ciHHV-6 have been misdiagnosed and unnecessarily treated with powerful and toxic antiviral agents based on a mistaken diagnosis of reactivated HHV-6. High persistent HHV-6 DNA levels in blood can be found in immunocompetent individuals with viral chromosomal integration. Analysis for integration is a necessary first step in distinguishing between ciHHV6 and HHV-6 reactivation.
The second necessary step for identifying HHV-6 reactivation in a ciHHV6 patient is confirmation of viral gene expression using mRNA detection. RT-PCR for mRNA can distinguish an active herpesvirus infection from a latent infection. In addition, it is difficult to evaluate response to antiviral therapy in a ciHHV-6 patient because the high level of DNA from ciHHV-6 overwhelms and masks viral DNA produced by reactivated virus. mRNA testing can be used to evaluate the efficacy of antiviral therapy in a ciHHV-6 patient.
The ciHHV-6 panel from Coppe Laboratories
ciHHV6 occurs in about 1% of the population and confounds the diagnostic interpretation of reactivated HHV-6 in solid organ and hematopoietic transplant recipients (SOT and HCT). In the case of an HCT recipient or donor who has undiagnosed ciHHV6, the evolution of chimerism due to stem cell engraftment can be misdiagnosed as HHV-6 reactivation during the early engraftment period and patients may be treated inappropriately. Conversely, in the case of pre-identified ciHHV6 HCT or SOT recipients, the high background level of DNA from integrated HHV-6 can mask HHV-6 reactivation and make it impossible to evaluate the efficacy of antiviral therapy.
The ciHHV-6 Test Panel from Coppe Laboratories can identify active infection in a ciHHV-6 individual.