Herpesviruses are a family of viruses that includes herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), roseolovirus, Kaposi sarcoma-associated herpesvirus, and Epstein-Barr virus (EBV).
The herpes virus enters the body through the mucous membranes of the respiratory and/or genital tract and causes lifelong latent infections in specific cells and tissues. Beta- and gamma-herpesviruses (CMV, EBV) target hematopoietic cells, and most alpha-herpesviruses (HSV-1, HSV-2, VZV) target peripheral neurons.
During the latent period, the infectious virus is not produced. Stress or suppression of immunity can lead to the reactivation of the herpes virus. The reactivated virus multiplies again on the mucous membrane and becomes contagious. Interferons are one of the most important factors that inhibit the reactivation of herpes and contribute to its transition to a latent state.
Interferons are signaling molecules that trigger antiviral protection. The first line of defense against viruses is innate immunity. On the surface of the innate immune system cells, there are pattern recognition receptors, with the help of which immune cells detect a virus that has entered the body. The cells trigger an antiviral response by activating the interferon system of types I and III (IFN) upon detecting the virus.
Interferon is a type III IFN-λ, which is expressed by epithelial cells of the mucous membranes. To trigger an antiviral response, IFN-λ binds to the IFNLR1 receptor, also expressed on mucous membranes. Therefore, IFN-λ is paramount for protection against viruses interacting with mucous membranes, particularly the herpes virus.
Interferon Type III Protects Against Herpesviruses
Herpesvirus infection, at least HSV-1 and HSV-2 infection, cause a significant IFN-III response. The type III interferon response promotes local antiviral protection against HSV:
- Type III interferons inhibit HSV replication in epithelial cells. Interestingly, IFN-λ exhibits a more powerful antiviral effect than IFN-alpha.
- In keratinocytes of the skin cells, IFN-III exhibits antiviral activity against HSV-1. HSV-1 is a neurotropic virus that causes latent infection in sensory neurons and can cause herpes simplex encephalitis in rare cases. Interferon type III suppresses HSV-1 infection in neurons and astrocytes.
- IFN-λ-1 and, to a lesser extent, IFN-λ-2 suppressed virus replication, viral gene expression, and protein production in human dermis cells infected with VZV.
- Recombinant IFN-λ-2 reduced infection with the herpes virus MuHV-4 by 65% in mouse lung epithelial cells that overexpressed the IFNLR1 receptor. More extended circulation of IFN-λ-2 declined upper respiratory tract infection, but not MuHV-4 lung infection. However, IFN-λ-2 could not block the genital reactivation of MuHV-4, although it delayed it.
Interferon-Λ To Prevent Herpes Simplex Virus
Approximately two-thirds of the world’s population is infected with HSV-1, and about 11% are infected with HSV-2. A vaccine against the herpes simplex virus has not yet been developed. However, recently Chinese scientists have proposed using IFN-λ as an adjuvant for a DNA vaccine against HSV-2. In a mouse study, IFN-λ-3 enhanced the expression of IFN-gamma, which plays a central role in the adaptive immune response to the herpes virus. IFN-λ-3 enhanced the protective response to the vaccine, reduced the viral load of HSV-2, and protected the genital tract from damage.
Interferon-Λ Can Both Enhance Tissue Damage and Cause An Antiviral Effect
Despite the limited range of cells that produce and respond to IFN-λ, it can cause local inflammation and tissue damage. For example, herpesviruses are found in periodontal pockets of patients with chronic or aggressive periodontitis. Herpesviruses trigger the IFN-III response. In comparison with healthy people, higher levels of IFN-λ are observed in the gum tissues of patients with chronic or aggressive periodontitis. It means that IFN-λ may be involved in developing chronic inflammation in periodontitis.
On the other hand, another study showed that IFN-λ-1 levels were lower in patients with periodontitis infected with HSV-1, HSV-2, CMV, and/or EBV compared with non-infected herpesvirus patients with periodontitis, which means that IFN-λ-1 can have an antiviral effect.
Conclusion
The herpes virus enters the body through the mucous membranes and causes a significant type III interferon response. IFN-III has an antiviral effect, but it can also increase inflammation and tissue damage caused by herpes. IFN-III suppresses herpesvirus replication and may slow its reactivation. Type III interferon may enhance the effectiveness of future herpesvirus vaccines.
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Reference
Herpesviruses and the Type III Interferon System
