Research Topic

Immuno-pathogenic aspects of human herpesvirus-6A or -6B (HHV-6A or HHV-6B) infection in autoimmunity, degenerative and other HHV-6A or HHV-6B-associated diseases

About this Research Topic

Several immune-mediated diseases are associated with viral etiopathologies. Of special interests are the large enveloped herpesviruses, like human herpesvirus-6A or -6B (HHV-6A or HHV-6B), with widespread prevalence, causing harmless or asymptomatic disease in the majority of the population, but potentially chronic inflammatory diseases and neuronal degeneration in a subset of susceptible individuals. The research topic concentrates on a possible immune-pathogenic role of HHV-6A or HHV-6B in autoimmunity, degenerative and other diseases. One example would be age-related macular degeneration (AMD), the leading cause of irreversible central blindness in elderly people. One of the earliest changes in the retina of AMD patients is the loss of CD46, a complement inhibitor, in the retinal pigment epithelial cells. Since HHV-6A uses CD46 as its receptor to enter cells, the virus could well play an etiologic role in AMD by infection of the retina leading to downregulation of CD46 and consequently to hyperactivation of the complement system in the eyes of susceptible individuals. Similar indications of viral interferences are of interest to be investigated in other chronic inflammatory and neurodegenerative diseases.

The goal of the Research Topic is to test the above hypothesis of an etiologic and immunopathogenic role of HHV-6A or HHV-6B. Research could extend to several HHV-6A or HHV-6B related diseases and thereby find common viral immuno-pathogenic mechanisms. To reach this goal, experimental and clinical, in vitro and in vivo evidence is needed as well as genetic and epidemiological studies. Further knowledge on these subjects would allow to plan for interventional studies looking for targeted preventive and therapeutic means to interfere with viral immunopathogenic mechanisms. Experiences would include HHV-6A-related and potentially related diseases like multiple sclerosis (MS), Hashimoto’s Thyroiditis (HT), Systemic Sclerosis (SSc) and (AMD), as well as HHV-6B-related diseases like epilepsy, encephalitis and issues regarding transplantation, to clarify the immunopathogenic mechanisms they have in common but also what makes them distinct. Of note, the prevalence of HHV-6A in different populations is still not known. Correlating HHV-6A prevalence with associated diseases would be of interest. It is also of importance to know that HHV-6A and HHV-6B can integrate into the host-cells chromosomes and can be reactivated later in lifetime, possibly through epigenetic modifications. Furthermore, HHV-6A and HHV-6B particles incorporate a variety of host cell proteins in the envelope taken from the host cell and can thus potentially direct the immune response against specific target tissues infected by the virus.

The themes addressed by this Research Topic include the following:
• searching for HHV-6A or HHV-6B DNA, epigenetic modification, viral proteins, altered gene expression profiles and HHV-6A or HHV-6B-encoded miRNA in pathology samples of AMD, MS, HT, AIDS, SSc, epilepsy, encephalitis and other diseases.
• studying the pathology in regards to the complement inhibitor and HHV-6A receptor CD46.
• studying the role of chromosomal integration and reactivation of HHV-6A or HHV-6B in relation to disease.
• studying other viral immuno-pathogenic mechanisms in HHV-6A or HHV-6B-related diseases like AMD, MS, HT, HIV/AIDS, SSc, epilepsy, encephalitis and other diseases.
• studying experimental infection of targeted host cells with HHV-6A or HHV-6B in vitro and mechanisms like complement inhibitor expression, autophagy and giving an overview of cell specific dynamic omics.
• studying animal models of HHV-6A or HHV-6B-induced diseases.
• evaluating the epidemiologic association between AMD and other HHV-6A-related diseases like MS, HT, SSc.

We welcome the submission of Original Research, Reviews, Mini-reviews, Opinion and Perspective articles.


Topic Editor Walter Fierz is President of the Swiss Association of the Diagnostic Industry (SVDI). The other Topic Editors declare no competing interests.


Keywords: human herpesvirus, HHV-6, age-related macular degeneration (AMD), degenerative diseases, viral immunology


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Several immune-mediated diseases are associated with viral etiopathologies. Of special interests are the large enveloped herpesviruses, like human herpesvirus-6A or -6B (HHV-6A or HHV-6B), with widespread prevalence, causing harmless or asymptomatic disease in the majority of the population, but potentially chronic inflammatory diseases and neuronal degeneration in a subset of susceptible individuals. The research topic concentrates on a possible immune-pathogenic role of HHV-6A or HHV-6B in autoimmunity, degenerative and other diseases. One example would be age-related macular degeneration (AMD), the leading cause of irreversible central blindness in elderly people. One of the earliest changes in the retina of AMD patients is the loss of CD46, a complement inhibitor, in the retinal pigment epithelial cells. Since HHV-6A uses CD46 as its receptor to enter cells, the virus could well play an etiologic role in AMD by infection of the retina leading to downregulation of CD46 and consequently to hyperactivation of the complement system in the eyes of susceptible individuals. Similar indications of viral interferences are of interest to be investigated in other chronic inflammatory and neurodegenerative diseases.

The goal of the Research Topic is to test the above hypothesis of an etiologic and immunopathogenic role of HHV-6A or HHV-6B. Research could extend to several HHV-6A or HHV-6B related diseases and thereby find common viral immuno-pathogenic mechanisms. To reach this goal, experimental and clinical, in vitro and in vivo evidence is needed as well as genetic and epidemiological studies. Further knowledge on these subjects would allow to plan for interventional studies looking for targeted preventive and therapeutic means to interfere with viral immunopathogenic mechanisms. Experiences would include HHV-6A-related and potentially related diseases like multiple sclerosis (MS), Hashimoto’s Thyroiditis (HT), Systemic Sclerosis (SSc) and (AMD), as well as HHV-6B-related diseases like epilepsy, encephalitis and issues regarding transplantation, to clarify the immunopathogenic mechanisms they have in common but also what makes them distinct. Of note, the prevalence of HHV-6A in different populations is still not known. Correlating HHV-6A prevalence with associated diseases would be of interest. It is also of importance to know that HHV-6A and HHV-6B can integrate into the host-cells chromosomes and can be reactivated later in lifetime, possibly through epigenetic modifications. Furthermore, HHV-6A and HHV-6B particles incorporate a variety of host cell proteins in the envelope taken from the host cell and can thus potentially direct the immune response against specific target tissues infected by the virus.

The themes addressed by this Research Topic include the following:
• searching for HHV-6A or HHV-6B DNA, epigenetic modification, viral proteins, altered gene expression profiles and HHV-6A or HHV-6B-encoded miRNA in pathology samples of AMD, MS, HT, AIDS, SSc, epilepsy, encephalitis and other diseases.
• studying the pathology in regards to the complement inhibitor and HHV-6A receptor CD46.
• studying the role of chromosomal integration and reactivation of HHV-6A or HHV-6B in relation to disease.
• studying other viral immuno-pathogenic mechanisms in HHV-6A or HHV-6B-related diseases like AMD, MS, HT, HIV/AIDS, SSc, epilepsy, encephalitis and other diseases.
• studying experimental infection of targeted host cells with HHV-6A or HHV-6B in vitro and mechanisms like complement inhibitor expression, autophagy and giving an overview of cell specific dynamic omics.
• studying animal models of HHV-6A or HHV-6B-induced diseases.
• evaluating the epidemiologic association between AMD and other HHV-6A-related diseases like MS, HT, SSc.

We welcome the submission of Original Research, Reviews, Mini-reviews, Opinion and Perspective articles.


Topic Editor Walter Fierz is President of the Swiss Association of the Diagnostic Industry (SVDI). The other Topic Editors declare no competing interests.


Keywords: human herpesvirus, HHV-6, age-related macular degeneration (AMD), degenerative diseases, viral immunology


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

31 August 2021 Abstract
21 December 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

31 August 2021 Abstract
21 December 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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