Cytomegalovirus and Epstein–Barr Virus Associations with Neurological Diseases and the Need for Vaccine Development

Abstract

Herpesviruses have been isolated from a wide range of hosts including humans—for which, nine species have been designated. The human herpesviruses are highly host adapted and possess the capacity for latency, allowing them to survive in the host for life, effectively hidden from the immune system. This ability of human herpesviruses to modulate the host immune response poses particular challenges for vaccine development but at the same time proves attractive for the application of human herpesvirus vaccines to certain spheres of medicine. In this review, congenital cytomegalovirus (CMV) infection and hearing loss will be described followed by a comment on the status of current vaccine development. Secondly, the association of Epstein–Barr virus (EBV) infection with multiple sclerosis (MS) and how EBV vaccination may be of benefit will then be discussed. Prevention of congenital CMV by vaccination is an attractive proposition and several vaccines have been evaluated for potential use. Particularly challenging for the development of CMV vaccines are the needs to prevent primary infection, reinfection, and reactivation at the same time as overcoming the capacity of the virus to generate highly sophisticated immunomodulatory mechanisms. Cost and the practicalities of administering potential vaccines are also significant issues, particularly for low- and middle-income countries, where the burden of disease is greatest. An effective EBV vaccine that could prevent the 200,000 new EBV-associated malignancies which occur globally each year is not currently available. There is increasing interest in developing EBV vaccines to prevent MS and, in view of the association of infectious mononucleosis with MS, reducing childhood infectious mononucleosis is a potential intervention. Currently, there is no licensed EBV vaccine and, in order to progress the development of EBV vaccines for preventing MS, a greater understanding of the association of EBV with MS is required.

PD-1 and PD-L1 Expression on Circulating Lymphocytes as a Marker of Epstein-Barr Virus Reactivation-Associated Proliferative Glomerulonephritis

“…The life cycle of EBV is particularly complex and the virus undergoes the latency phase during which it expresses several genes impacting oncogenesis [44][45][46][47]. Recent studies have shown that EBV DNA is present in large quantities in patients with autoimmune diseases of several etiologies [48,49]. However, there are no proofs on the effect of EBV reactivation on the expression of PD-1 and PD-L1 antigens in patients with primary GN.…”

Nutraceutical Curcumin with Promising Protection against Herpesvirus Infections and Their Associated Inflammation: Mechanisms and Pathways

“…The extensive use of these drugs in the therapy has formed the problem of drug resistance, leading to noticeable treatment failure [ 32 , 33 , 34 ]. While various ongoing studies have attempted to produce herpesvirus vaccination, no vaccines or antiviral drugs have been approved for the prevention of herpesvirus infections so far [ 35 , 36 ]. Therefore, there is an urgent demand for developing novel antiherpetic drugs that could effectively cure or prevent herpesvirus infections with less resistance, diminished adverse effects, low toxicity, and improved stability [ 37 , 38 ].…”

Apoptosis Disorder, a Key Pathogenesis of HCMV-Related Diseases

“…Moreover, several studies have shown that HCMV infection causes the occurrence and progression of several chronic diseases, including autoimmune disease (AID) [ 33 ], tuberculosis [ 34 ], atherosclerosis [ 7 ], mental disorders [ 35 ], age-related macular degeneration (AMD) [ 36 ], pneumonitis, and myocarditis [ 37 ]. In particular, many studies have revealed that HCMV infection is related to various cancers, such as cervical cancer [ 38 ], breast cancer [ 39 ], colorectal cancer [ 40 ], ovarian cancer [ 41 ], prostate cancer [ 42 ], squamous cell carcinoma [ 43 ], lymphoma [ 44 ], glioblastoma [ 45 ], medulloblastoma [ 46 ], and neuroblastoma [ 47 ], as well as poor outcomes. A list of HCMV-related diseases is provided in Figure 1 .…”