Background
CMV is the largest type of human herpesvirus and is a double-stranded DNA virus. The diameter of the complete virus particle is 200-300nm. Under the electron microscope, from outside to inside, there are a lipid envelope containing a variety of glycoproteins, a membrane, an icosahedral stereosymmetric capsid, and an internal nucleoprotein core containing its genome. The lipid envelope contains glycoproteins, which can induce the production of neutralizing antibodies. The currently discovered CMV envelope glycoproteins include glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein O, etc. The CMV envelope is located between the icosahedral capsid and the envelope. It is a unique structure of herpes viruses. Its envelope protein contains abundant phosphorylated protein pp65, which can induce a strong cellular immune response and plays an important role in virus assembly, gene regulation and it plays a role in changing host cell metabolism and other aspects. In addition to constituting the viral capsid, the CMV capsid protein also serves to anchor viral DNA. The genome is a 64nm linear double-stranded DNA molecule containing non-overlapping open reading frames of more than 230 proteins; one of these proteins is DNA polymerase, which plays an integral role in viral replication and is the component of all currently approved the main target of antiviral drugs. CMV infection elicits strong virus-specific CD 4+ and CD8+ T cell responses. The body can produce specific antibodies against different antigens of CMV, with IgG indicating past infection and IgM indicating acute or recent infection. Studies have found that the humoral immune response generated by the body against CMV mainly targets the viral envelope glycoprotein gB, while the cellular immune response mainly targets the envelope protein pp65.
Figure 1. HCMV-induced modulation of the host immune system.(Source: El Baba R, et al., 2021)
CMV has a typical herpes virus morphology and its DNA structure is similar to HSV, but is 5% larger than HSV. This virus is highly species-specific to the host or cultured cells. Human cytomegalovirus (HCMV) can only infect humans and proliferate in human fibroblasts. The virus proliferates slowly in cell culture and has a long replication cycle. It takes 30 to 40 days for initial isolation and culture before cell lesions appear, which are characterized by enlarged cells, enlarged nuclei, and the appearance of large-scale viruses acidic inclusion bodies surrounded by a "halo" in the nucleus. The body's cellular immune function plays an important role in the occurrence and development of CMV infection. People with cellular immunity deficiency can lead to severe and long-term CMV infection, and further suppress the body's cellular immunity, such as decreased activity of killer T cells, NK Reduced cell function, etc. After primary infection with CMV, the body can produce specific antibodies and killer T lymphocytes and activate NM cells. Antibodies have limited CMV replication capacity and have certain resistance to reinfection with the same strain, but they cannot resist activation of endogenous latent viruses and exogenous infection with other different strains of CMV. The greatest antiviral effect can be exerted through specific killer T lymphocytes and antibody-dependent cytotoxic cells.
Preliminary diagnosis can be made by centrifuging saliva, urine, cervical secretion and other specimens, and using Giemsa staining to examine the exfoliated cells under a microscope to detect giant cells and intranuclear and intraplasmic eosinophilic inclusions. For isolation and culture, the specimen can be inoculated into human embryonic lung fibroblasts. Due to the long growth cycle of CMV, cell lesions appear slowly. For rapid diagnosis, the infected cells cultured for 24 hours can be fixed, and DNA probes can be used for in situ hybridization and detection. ELISA is used to detect lgM antibodies and lgG antibodies, which is suitable for early infection and epidemiological investigations. IgG antibodies can persist throughout life, and lgM antibodies are associated with acute infections. Whether it is an initial infection or a recurrent infection, when there is viremia, peripheral blood mononuclear cells can be extracted with dextran solution, made into smears, and CMV monoclonal antibodies are added, and immunoenzyme or fluorescent staining is used to detect intracellular antigens. In recent years, the application of Western blotting and molecular hybridization technology to directly detect CMV antigen and DNA from urine and various secretions is a rapid, sensitive and accurate method.
Alternative Names
UL32 protein
CMV tegument protein pp150
Tegument protein UL32
Human cytomegalovirus phosphoprotein 150
HCMV pp150
References
- 1. El Baba R, et al., Immune Landscape of CMV Infection in Cancer Patients: From "Canonical" Diseases Toward Virus-Elicited Oncomodulation. Front Immunol. 2021, 12:730765.