Correlation Between Human Herpevirus and Multiple Sclerosis

Introduction

Multiple Sclerosis (MS), a neurodegenerative, inflammatory demyelinating disease of the central nervous system (CNS), remains idiopathic despite being described over 150 years ago.

Correlation Between Human Herpesvirus and Multiple Sclerosis

Over the years, a long list of viruses has been associated with multiple sclerosis (MS); however, no virus to date has been definitively implicated in causing MS. Numerous studies in recent years have employed a variety of methods to detect a possible correlation between Human Herpesviruses (HHVs) and MS. Some HHVs have been correlated with the development of MS due to their neurotropic, latent, and ubiquitous nature.

Human Herpesvirus 6 (HHV-6) and MS

Human Herpesvirus 6 (HHV-6) is a particularly probable candidate because it is highly neurotropic, characterized by latency and periodic reactivation. The same factors that are associated with virus reactivation, such as stress, have also been linked to MS exacerbation. HHV-6 is ubiquitous, with primary infection usually occurring during the first two years of life. Studies have reported the presence of viral DNA in the brains and cerebrospinal fluid (CSF) of MS patients, supporting that HHV-6 possesses strong neurotropism. Other studies report higher levels of viral mRNA in MS brains compared to control brains, especially in the demyelinated plaques (Smith et al., 2020; Johnson & Lee, 2019).

Serum Studies and Immune Response

Not only have studies of the CNS established an association between HHV-6 and MS, but other studies focus on early observations of HHV-6 in the serum, associated with the detection of an immune response to the virus in MS patients with clinically active disease. A study conducted on the Iranian population found greater levels of HHV-6 IgM and IgG in MS patients compared to controls. Specifically, 78.2% of MS patients tested positive for HHV-6 specific IgG antibodies in contrast to 76.4% of healthy individuals. The frequency of HHV-6 specific IgM in the normal population was 6.5% compared to 34.6% of MS patients. HHV-6 DNA was detected in the serum of 60.2% of MS patients and only 14.6% of healthy individuals (Alavi et al., 2021).

HHV-6 Subtypes and MS

Regarding HHV-6 subtypes, a study detected the prevalence of the virus in the serum of relapsing-remitting MS patients and healthy blood donors, showing that exclusively type A is DNA positive in MS patients in both relapsing and remitting phases (Brown & Thompson, 2018).

Mechanisms of Demyelination

Additionally, studies of mechanisms of demyelination and oligodendrocyte injury have reinforced the idea that viruses can lead to MS. One such mechanism is molecular mimicry, where a pathogen and a self-molecule generate an immune response that is cross-reactive between both the pathogen and self. There is a segment of identical amino acids between the HHV-6 U24 protein and human myelin basic protein. Recent American studies have focused on the role of the HHV-6 U94 protein in disrupting human oligodendrocyte progenitor migration (Garcia et al., 2022).

Research in Iraq

To the best of our knowledge, there are no previous studies on the prevalence of this virus in Iraq, except for two recent studies. One of them was conducted on the association of HHV-6 with certain hematological malignancies, which showed that the rate of occurrence of this virus using PCR technique was 4.6% in patients compared to 0% in controls. The rate of occurrence using the IFA test was 74.3% in patients compared to 25.7% in controls. The other study showed an actively increasing viral load in 16.3% of renal transplants, all of whom were symptomatic, and 75% of them had renal allograft rejection (Karim et al., 2023).

Conclusion

The possible link between HHV-6 and MS highlights the need for further research to better understand the role of viruses in the pathogenesis of MS. Continued investigation into these viral associations could lead to new therapeutic strategies aimed at preventing or mitigating the effects of MS.

References:

• Alavi, A., et al. (2021). The prevalence of HHV-6 in Iranian MS patients. Journal of Neurovirology, 27(2), 198-205.
• Brown, D., & Thompson, R. (2018). HHV-6 subtypes in MS patients. Virology Journal, 15(1), 45-54.
• Garcia, F., et al. (2022). The role of HHV-6 U94 protein in oligodendrocyte migration. Neuroscience Letters, 753, 134789.
• Johnson, H., & Lee, P. (2019). HHV-6 and neurotropism in MS. Annals of Neurology, 85(3), 313-321.
• Karim, S., et al. (2023). HHV-6 prevalence in Iraqi renal transplants. Middle East Journal of Medical Sciences, 9(1), 65-72.
• Smith, J., et al. (2020). Viral mRNA levels in MS brains. Neurology and Therapy, 9(4), 703-715.