Human Herpesvirus-6A/B Binds to Spermatozoa Acrosome and Is the Most Prevalent Herpesvirus in Semen from Sperm Donors

Abstract

An analysis of all known human herpesviruses has not previously been reported on sperm from normal donors. Using an array-based detection method, we determined the cross-sectional frequency of human herpesviruses in semen from 198 Danish sperm donors. Fifty-five of the donors had at least one ejaculate that was positive for one or more human herpesvirus. Of these 27.3% (n = 15) had a double herpesvirus infection. If corrected for the presence of multiple ejaculates from some donors, the adjusted frequency of herpesviruses in semen was 27.2% 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%; HHV-7 in 4.2%, whereas none of the samples had detectable VZV or HHV-8. Subsequently, we examined longitudinally data on ejaculates from 11 herpesvirus-positive donors. Serial analyses revealed that a donor who tested positive for herpesvirus at one time point did not necessarily remain positive over time. For the most frequently found herpesvirus, HHV-6A/B, we examined its association with sperm. For HHV-6A/B PCR-positive semen samples, HHV-6A/B could be detected on the sperm by flow cytometry. Conversely, PCR-negative semen samples were negative by flow cytometry. HHV-6B was shown to associate with sperm within minutes in a concentration dependent manner. Confocal microscopy demonstrated that HHV-6B associated with the sperm head, but only to sperm with an intact acrosome. Taken together, our data suggest that HHV-6A/B could be transported to the uterus via binding to the sperm acrosome. Moreover, we find a 10 times higher frequency of HHV-7 in semen from healthy individuals than previously detected. Further research is required to determine the potential risk of using herpesvirus-positive donor semen. Longitudinally analyses of ejaculate series indicate that implementation of quarantine for a donor shown to shed a herpesvirus is not a tenable solution.

Roseolovirus molecular biology: recent advances

“…Other cell types such as monocytes, dendritic cells, astrocytes, and glial cells are permissive for infection. HHV6A and HHV-6B can bind to the sperm acrosome, providing a possible route to germline integration [19]. The ability of HHV-6A and HHV-6B to infect olfactory-ensheathing glial cells that are present in the nasal cavity may provide a route to the central nervous system [20].…”

Describing the Silent Human Virome with an Emphasis on Giant Viruses

“…Indeed, Csoma et al [112] detected KI virus and WU virus in the urine of renal transplants but not in the control groups. Moreover, immunosuppression due to pregnancy led to a higher prevalence of BK virus in urine samples in pregnant women compared to non-pregnant women [113]. …”

“…In this case it appears that some herpesviruses, such as human Herpesvirus 6 A/B or the Cytomegalovirus, were able to attach to the sperm head with an intact acrosome [108,113]. Thus, given the potential risk some herpesviruses may represent to the newborns, additional research is required to evaluate the impact of this asymptomatic shedding from herpesvirus-positive donor semen.…”

Seminal shedding of human herpesviruses

“…Except for one study from Greece [23], there is agreement that VZV is neither present in semen from fertility-clinic attendants (Germany) [11], nor from men of couples undergoing IVF treatment (Spain) [22], or from healthy sperm donors (Denmark) [18]. Taken together, the evidence indicates that VZV is not present in semen, perhaps reflecting the infrequency of VZV reactivation occurring from the ganglia rather than immune cells.…”

“…Chen et al found HHV-6A/B in 2.0% of infertility patients from China [14], whereas Michou et al detected HHV-6A/B in 8.2% of 109 men from couples undergoing IVF treatment in Spain [22]. A slightly higher prevalence of 13.5% was seen by Kaspersen et al in semen from Danish sperm donors [18] (Table 2), suggesting that the prevalence of HHV-6A/B is not increased among patients attending a fertility clinic. A remarkably high prevalence of 66.8% among men attending a fertility clinic on Crete has been reported by Neofytou et al using nested PCR [23].…”