I. Biological characteristics
Epstein-Barr virus is similar to other herpes viruses in shape, with a diameter of 180nm. Its basic structure consists of nucleoid, capsid and capsule. Nucleoid is a dense substance with a diameter of 45nm, which mainly contains double-stranded linear DNA. Its length varies with different strains, with an average of 17.5× 104 bp and a molecular weight of 108. The capsid is a three-dimensional symmetrical icosahedron, which consists of 162 shell particles. The envelope is composed of the nuclear membrane of infected cells, which has the membrane glycoprotein encoded by virus and has the function of recognizing EB virus receptors on lymphocytes and fusing with cells. In addition, there is a protein coating between the capsule and the shell.
Epstein-Barr virus can only proliferate in B lymphocytes, which can be transformed and inherited for a long time. Virus-infected cells have the genome of EBV and can produce many antigens, including EBV nuclear antigen (EBNA), early antigen (EA), membrane antigen (MA), capsid antigen (VCA) and lymphocyte recognition membrane antigen (LYDMA). Epstein-Barr virus has been lurking in lymphocytes for a long time, dissociated in cytoplasm in the form of circular DNA, and integrated into chromosomes.
Second, immunity.
People infected with EBV can induce anti-EBNA antibody, anti-EA antibody, anti-VCA antibody and anti-MA antibody. It has been proved that antibodies against MA antigen can neutralize EBV. Humoral immune system can prevent exogenous virus infection, but it can't eliminate latent virus infection. It is generally believed that cellular immunity (such as cytotoxic reaction of T lymphocytes) plays a key role in "monitoring" virus activation and eliminating transformed B lymphocytes.
Three. Microbial diagnosis
It is difficult to isolate and culture EBV, and serological methods are generally used to assist diagnosis. Conditional laboratories can use nucleic acid hybridization and PCR to detect EBV genome and its expression products in cells.
Fourth, related diseases caused by EB virus infection:
(1) Non-tumor diseases
1. infectious mononucleosis
Most patients developed IM after being infected with EBV. The virus was first discovered as the pathogen of IM in 1968, and was later confirmed by seroepidemiological study. This disease is the only known disease directly caused by EBV, which has the following theoretical basis: (1) This virus can only grow and proliferate in cells of lymphatic reticular system; (2) The virus can stimulate the proliferation of lymphocytes in the process of culture; (3)EBV； Can be cultured from acute peripheral blood lymphocytes; (4) High titer of EBV-specific antibody in patients' serum can exist for a long time; (5) People without this specific antibody are prone to this disease, and people with positive antibodies do not get sick. The main symptoms of IM are: fever, sore throat, rash and swollen lymph nodes in liver and spleen. The changes of blood system can involve three systems, but there are many changes of white blood cells, most of which are the increase of total white blood cells and abnormal lymphocytes.
2. Oral leukoplakia
Most of them occur in patients with immunodeficiency. EBV proliferation antigen and viral DNA can be detected in the upper layer of diseased epithelium.
3.x chromosome associated lymphoproliferative syndrome (XLP)
It is a rare immunodeficiency disease related to X chromosome, which is only found in boys. EBV infection often leads to fatal IM or malignant lymphoma.
4. Virus-associated polycythemia
This is reactive histiocytosis. The main clinical manifestations are high fever, lymphadenopathy of liver and spleen, abnormal liver function, disorder of coagulation function, decrease of total number of peripheral blood cells, no abnormality of lymphocytes, and phagocytosis of red blood cells by bone marrow. Serological examination showed that anti-VCA-IgG, anti-VCA-IgM and anti-EA-IgG were increased, and anti-EBNA antibody was lacking, which was consistent with the acute infection of EB virus.
(2) Tumor diseases
1. Burkitt lymphoma
EBV was first isolated from Burkitt's lymphoma cells of African children by British virologists Epstein and Barr in 1964, and its correlation with Burkitt's lymphoma is beyond doubt. Burkitt's lymphoma can be divided into endemic and sporadic. The former is mainly seen in children in Central Africa, and the lesions are more common in jaw, orbit, central nervous system and abdomen. Small undifferentiated B cells are its morphological characteristics. Almost all endemic cases are related to EBV; However, only 15% ~ 20% of sporadic Burkitt's lymphoma is related to EBV, and many new subtypes of EBV-related lymphoma have been found in recent years.
2. Hodgkin's disease
Traditionally, it is divided into four types: lymphocyte-dominated type, mixed cell type, nodular sclerosis type and lymphocyte depletion type. Among them, the mixed type is closely related to EBV, and the virus detection rate can reach 96%, while the detection rates of nodular sclerosis type and lymphocyte-dominated type are 34% and 10% respectively. The close relationship between HD and EBV varies with region and age. The positive rate of EBV in HD in Latin American countries such as Peru, Honduras and Mexico is higher than that in Europe and America. In China, more than 90% of children's HD is related to EBV, especially for children under 10. EBV is detected in 95% of children, which has nothing to do with tissue subtype. Many data show that the risk of HD in children with IM is five times that in the control group.
3. Nasopharyngeal Carcinoma (NPC)
NPC is the most common malignant tumor closely related to EBV, and it is also the most reported one. Southern China is a high incidence area of NPC. Among the early symptoms of nasopharyngeal carcinoma in children, the symptoms caused by the primary nasopharyngeal lesion are not obvious, and the sick children do not understand the discomfort caused by it. In addition, general clinicians do not know enough about children's cases, and it is easy to miss the diagnosis. Although EBV is closely related to the occurrence of NPC, there is no animal experiment to prove that EBV alone causes epithelial cancer, nor can it be proved that EBV is the only cause of NPC.
(3) Other diseases
In addition to the above diseases closely related to EBV, EBV infection has also been found in some pediatric diseases, such as leiomyosarcoma, large cell anaplastic lymphoma, malignant histiocytosis, rheumatoid arthritis, Kawasaki disease, glomerulonephritis, nephrotic syndrome, viral myocarditis, pericarditis, acute idiopathic thrombocytopenic purpura, multiple sclerosis, viral encephalitis, Guillain-Barre syndrome and aplastic anemia.
Frontiers and prospects of verb (abbreviation of verb) research;
At present, there are two kinds of vaccines. One is a vaccinia vaccine expressing EBV gp320 and HBsAg at the same time, which is constructed by genetic engineering method in China and is mainly used in high incidence areas of nasopharyngeal carcinoma. The other is the purified virus gp320 membrane protein vaccine, which is currently being inoculated in small and medium scale among British college students to see if the vaccine can reduce the incidence of infectious mononucleosis. Acyclic guanosine (AC) and propoxyguanosine (DHPG) can inhibit EBV replication, and both of them have certain curative effects.