Inherited chromosomally integrated HHV-6A and its potential role in unexplained infertility: the first clinical case from India—a case report

Background Human herpesvirus-6, double stranded DNA virus with 2 variants, has the ability to integrate into the human chromosome, including the germline leading to a condition called as inherited chromosomally integrated HHV-6 (iciHHV-6). This integrated form of HHV-6 (variant A) has been detected in the endometrium and linked to unexplained infertility, but its clinical significance remains unclear. Therefore, it becomes crucial how the virus transitions between the latency and active states in the reproductive tissue. The limited global literature on this topic, highlights the need for further investigation . Case We describe a case of a 22-year-old nulliparous woman of South Asian ethnicity with a 4-year history of primary unexplained infertility. Routine infertility workup including the hormonal profile, semen analysis, transvaginal ultrasonography and tubal patency assessment were normal. As a part of the research protocol HHV-6 testing was performed, which revealed the presence of HHV-6 DNA in the endometrial biopsy, serum, plasma and PBMCs of the patient. Sequencing results showed the presence of HHV-6A variant, aligning with a variant showing integration at 10q. Droplet digital PCR in the biopsy further confirmed chromosomal integration of HHV-6. Transcriptional analysis detected only latent transcripts with no evidence of active viral replication. Notably, the patient subsequently conceived. Conclusions This case suggests a possible association of iciHHV-6-A and infertility; however, a causal relationship cannot be established. Although only latent transcripts were identified at the time of diagnosis, the findings indicate that the presence of iciHHV-6A alone may not be sufficient to impair fertility. Further studies are required to understand the plausible mechanism as to what triggers the reactivation of iciHHV-6 and its further impact on reproductive health.