Human Herpetic Viruses and Immune Profiles
Innate Immunity in Health and Disease [Working Title]
Herpesviruses are large, spherical, enveloped viral particles with linear double-stranded DNA genome. Herpesvirus virion consists of an icosahedral capsid containing viral DNA, surrounded by a protein layer called tegument, and enclosed by an envelope consisting of a lipid bilayer with various glycoproteins. Herpesviruses persist lifelong in their hosts after primary infection by establishing a latent infection interrupted recurrently by reactivations. The Herpesviridae family is divided into
... y is divided into three subfamilies; α-herpesviruses, β-herpesviruses, and γ-herpesviruses based on the genome organization, sequence homology, and biological properties. There are eight human herpes viruses: Herpes simplex virus type 1 and 2 (HSV-1, −2) andVaricella-zoster virus (VZV), which belong to the α-herpesvirus subfamily; Human cytomegalovirus (HCMV), and Human herpesvirus type 6 and 7 (HHV-6,HHV-7), which belong to the β-herpesvirus subfamily; and Epstein–Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) or Human herpesvirus 8 (HHV-8), which belong to the γ-herpesvirus subfamily. Within this chapter, we summarize the current knowledge about EBV and CMV, regarding their genome organization, structural characteristics, mehanisms of latency, types of infections, mechanisms of immune escape and prevention. Epstein–Barr Virus (EBV) genome encodes over 100 proteins, of which only (30) proteins are well characterized, including the proteins expressed during latent infection and lytic cycle proteins. Based on major variation in the EBNA-2 gene sequence, two types of EBV are recognized, EBV type 1 and 2. Epstein–Barr virus types occur worldwide and differ in their geographic distribution depending on the type of virus. EBV spreads most commonly through bodily fluids, especially saliva. However, EBV can also spread through blood, blood transfusions, and organ transplantations. The EBV is associated with many malignant diseases such as lymphomas, carcinomas, and also more benign such as infectious mononucleosis, chronic active infection. The EBV has also been suggested as a trigger/cofactor for some autoimmune diseases. Overall, 1–1.5% of the cancer burden worldwide is estimated to be attributable to EBV The latently infected human cancer cells express the most powerful monogenic proteins, LMP-1 and LMP-2(Latent Membrane Protein-1,-2), as well as Epstein–Barr Nuclear Antigens (EBNA) and two small RNAs called Epstein–Barr Encoded Small RNAs (EBERs). The EBV can evade the immune system by its gene products that interfering with both innate and adaptive immunity, these include EBV-encoded proteins as well as small noncoding RNAs with immune-evasive properties. Currently no vaccine is available, although there are few candidates under evaluation. Human cytomegalovirus (HCMV) is a ubiquitous beta herpesvirus type 5 with seroprevalence ranges between 60 to 100% in developing countries. CMV is spread from one person to another, usually by direct and prolonged contact with bodily fluids, mainly saliva, but it can be transmitted by genital secretions, blood transfusion and organ transplantation. In addition, CMV can be transmitted vertically from mother to child. CMV infection can result in severe disease for babies, people who receive solid organ transplants or bone marrow/stem cell transplants and people with severe immune suppression such as advanced human immunodeficiency virus (HIV) infection. The HCMV has several mechanisms of immune system evasion. It interferes with the initiation of adaptive immune responses, as well as prevent CD8+ and CD4+ T cell recognition interfering with the normal cellular MHC Class I and MHC Class II processing and presentation pathways. Challenges in developing a vaccine include adeptness of CMV in evading the immune system. Though several vaccine candidates are under investigation.