Does HHV-6 infection of the sperm contribute to infertility?

Does HHV-6 infection of the sperm contribute to infertility?

Researchers from Denmark have identified HHV-6A/B in 13.5% of semen samples from 198 sperm donors, a significantly higher prevalence than any other herpesvirus detected in the study. In addition, the group has shown that HHV-6B binds specifically to the acrosome of sperm, suggesting that the virus could be transported to the uterus via this binding mechanism.

Overall, 55 of the 198 donors (27.2%) had at least one sample test positive for one or more herpesviruses, with HSV-1 in 0.4%, HSV-2 in 0.1%, EBV in 6.3%, HCMV in 2.7%, HHV-6A/B in 13.5%, and HHV-7 in 4.2%.

Flow cytometry analysis demonstrated the binding of HHV-6A/B antibodies to the sperm of all HHV-6A/B PCR positive semen samples, but in none of the HHV-6A/B-negative samples (p<.008). Confocal microscopy further identified the sperm acrosome as the binding site for HHV-6B, and staining with PSA demonstrated that HHV-6B only bound sperm with an intact acrosome. These findings suggest that the sperm acrosome contains a receptor for HHV-6B, which has yet to be identified.

While the consequences of herpesviruses on sperm quality and reproduction have yet to be fully elucidated, the authors point out that a previous study has suggested HHV-6A/B infection may predispose individuals to spontaneous abortion (Ando 1992). In the previous study, Ando et al showed that HHV-6 serum IgG and IgM antibody titers were greatly increased in patients with spontaneous abortions occurring at 6-12 weeks of pregnancy compared to normal pregnant women. HHV-6 antigen was also detected in abortive villous tissue of patients with HHV-6 IgM antibodies. Another recent study suggests that the type of herpesviruses found in semen may vary by region. In the study, 39% of sperm samples from 153 Chinese infertile men were found to be positive for one or more herpesviruses, with the largest percentages found for HSV-1 and CMV (Chen 2013).

Whether HHV-6A/B may cause complications due to congenital infection similar to those associated with HCMV remains unknown. In a statement released to the HHV-6 Foundation, Dr. Hollsberg reiterated that it is simply not yet known “whether sperm-associated HHV-6A/B is infectious.” However, he did confirm that the magnitude of such a finding would be very serious, further commenting that…

“…HHV-6 infection is known to inhibit p53 functions. A previous paper (Hu 2007) has established that p53 regulates maternal reproduction through secretion of a cytokine named LIF. Thus, if HHV-6A/B is able to cause infection in the uterus, it is conceivable that this infection could interfere with production of this cytokine and thus reproduction.  However, for now, this matter is pure speculation.”

For more information, read the full article from Dr. Per Hollsberg et al.