[5] HHV-6B primary infection is the cause of the common childhood illness exanthema subitum (also known as roseola infantum or sixth disease).

Additionally, HHV-6B reactivation is common in transplant recipients, which can cause several clinical manifestations such as encephalitis, bone marrow suppression, and pneumonitis.

In the context of infertility, this discovery underscores the importance of targeted testing for HHV-6A within the uterine environment, as the virus was not detected in the bloodstream of the affected individuals.

Effective diagnosis, therefore, requires tests that are capable of distinguishing between active and latent HHV-6A infections specifically in endometrial tissue, highlighting the need for tissue-specific viral detection methods in assessing and managing infertility associated with HHV-6A.

[9] A 2018 study found 37% of women experiencing recurrent implantation failure after IVF/ET had HHV-6A in their endometrial biopsies, compared to 0% in control groups.

It is possible to choose antiviral therapies and non-hormonal approaches for women with unexplained infertility characterized by HHV-6A to increase their pregnancy rate.

[11] The table below presents a comprehensive overview of various diagnostic tests used to detect human herpesvirus 6 (HHV-6), detailing their ability to distinguish between active and latent infections.

During 1986, Syed Zaki Salahuddin, Dharam Ablashi, and Robert Gallo cultivated peripheral blood mononuclear cells from patients with AIDS and lymphoproliferative illnesses.

The distinction was warranted due to unique restriction endonuclease cleavages, monoclonal antibody reactions,[17] and growth patterns.

[14] The virion's outer portion consists of a lipid bilayer membrane that contains viral glycoproteins and is derived from that of the host.

[25] The genetic material of HHV-6 is composed of linear (circular during an active infection), double stranded DNA which contains an origin of replication, two 8–10 kb left and right direct repeat termini, and a unique segment that is 143–145kb.

These conserved genes code for proteins that are involved in replication, cleavage, and packing of the viral genome into a mature virion.

[33] The extracellular region of CD46 contains four short consensus repeats of about 60 amino acids that fold into a compact beta-barrel domain surrounded by flexible loops.

While their precise interaction has not yet been determined, the second and third SCR domains have been demonstrated as required for HHV-6 receptor binding and cellular entry.

During the year 2011, researchers at the National Institutes of Health attempted to elucidate the then unknown method whereby HHV-6a gains entry into the nervous system.

[21] They suspected this association as a result of OECs having properties similar to those of astrocytes, another type of glial cell that was previously identified as being susceptible to HHV-6 infection.

[40] For instance, the U94 protein is believed to repress genes that are involved in cellular lysis (apoptosis) and also may aid in telomeric integration.

[28] A study published in The Journal of Infectious Diseases in 2024 investigated the reactivation of inherited chromosomally integrated human herpesvirus 6 (iciHHV-6B) in a liver transplant recipient and its impact on the graft.

Several studies also have shown that HHV-6 infection increases production of inflammatory cytokines that enhance in vitro expression of HIV-1, such as TNF-alpha,[44] IL-1 beta, and IL-8.

[45] A more recent in vivo study shows HHV-6A coinfection to dramatically accelerate the progression from HIV to AIDS in pigtailed macaques.

[18][49] Studies have found seroprevalence varying "from approximately 39 to 80% among ethnically diverse adult populations from Tanzania, Malaysia, Thailand, and Brazil.

The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time PCR.

HHV-6 has been reported in multiple sclerosis patients[52] and has been implicated as a co-factor in several other diseases, including chronic fatigue syndrome,[53] AIDS,[54] and temporal lobe epilepsy.

[55] Multiple sclerosis (MS) is an autoimmune and inflammatory disorder of the nervous system that results in demyelination of axons in the brain and spinal cord.

The first study to specifically investigate HHV-6-related demyelination appeared in the literature during 1996, when a previously healthy 19-month-old child developed acute encephalopathy.

Early on in the development of this hypothesis (2002), Italian researchers used the HHV-6a variant along with bovine myelin basic protein to generate cross-reactive T cell lines.

[61] A study of 259 patients with a "CFS-like" illness published shortly after HHV-6 was discovered used primary lymphocyte cultures to identify people with active replication of HHV-6.

Natural killer cells specific for HHV-6A, and high uterine levels of certain cytokines, were also found in the endometrium of the infertile women positive for HHV-6A.

[75] The typical methods whereby viruses initiate oncogenesis involve suppressing the host's immune system, causing inflammation, or altering genes.

[82] There are no pharmaceuticals approved specifically for treating HHV-6 infection, although the usage of Cytomegalovirus treatments (valganciclovir, ganciclovir,[83] cidofovir, and foscarnet) have shown some success.