Human T-lymphocyte virus infection

Introduction to human T lymphocyte infection Human-lymphotropic virus (HTLV) is a tumorigenic RNA virus belonging to the subfamily Jentiviridae, which can be divided into HTLV-I type and HTLV-II type. Recently, it has been found that the virus can cause more in humans. Diseases: HTLV-I can cause adult T cell leukemia/lymphoma (ATL), tropical spastic paraplegia/HTLV-associated myelopathy, etc.; HTLV-II and T- It is associated with diseases such as T-hairycell/largegranulocyticleukemia. basic knowledge The proportion of illness: 0.001% Susceptible people: no special people Mode of infection: unsterilized instruments for blood transfusion and injectable sexual intercourse Complications: portal hypertension, ascites, pleural effusion

The cause of human T lymphocyte virus infection

Causes:

HTLV is a retrovirus containing RNA and reverse transcriptase. It is a tumorigenic RNA virus. Under electron microscope, the virus particles are spherical and 100 nm in diameter. The inner core is composed of structural proteins, and the core shell and matrix (also known as The P15, P24 and P19GAG proteins surround the viral RNA and polymerase, and the outer layer is the viral envelope glycoprotein (surface and transmembrane glycoprotein, called GP46 and GP21, respectively) embedded in the bilayer lipid membrane. The viral genome is 30S. ~35S positive-stranded single-stranded RNA, about 10kb in length, has reverse transcriptase activity, and the genome is arranged in the order of 5'3' as gag-pol-env three structural genes and tax, rex two regulatory genes, LTR (long terminal repeat: R, U5, U3) at both ends, 65% nucleotide homology in the total sequence of HTLV-I and HTL-II, but lowest homology in the LTR sequence (30%) It is the highest (75% to 80%) in the 3'tax/rex regulatory gene.

HTLV gene coding: 1gag gene encodes p19, p24, p15 antigen; 2pol gene encodes reverse transcriptase (p95), Rnase H and integrase; 3env gene encodes glycoprotein (GP61, GP69) to bind to CD4 And further cleavage is GP46 and GP21, the former is distributed on the cell surface, the latter is a transmembrane protein; 4 such virus has a unique part at the 3' end of the gene, called pX, including four, namely X-I, X -II, X-III and X-IV, wherein X-III and X-IV encode the regulatory genes rex (p27rex, p26rex) and tex (p40tax, p37tax) in HTLV-I and HTLV-II, respectively. HTLV is not strong in resistance, it is easily inactivated by heat, dryness, sunlight, and fat solvent in the external environment, but it is stable at low temperature. The refrigerator can be stored in a refrigerator at -70 °C in 20% fetal bovine serum for a long time.

Pathogenesis:

After entering the human body, HTLV invades cells through the binding of envelope glycoprotein molecules to CD4 molecules on CD4 T cells in blood and tissues. Its genome forms proviral DNA under the action of reverse transcriptase and is located at many sites on the host cell chromosome. Integration, the proliferation of infected T cells, and finally developed into T cell leukemia.

The specific mechanism of HTLV-I virus-induced adult T-cell leukemia/lymphoma is not fully understood. In recent years, it has been considered that P40XI and P37XII, which are encoded by the tax-like gene, have a trans-acting activator and P40XI as a trans-acting factor. (trans-acting factor) activates promoters and enhancers in long terminal repeats (LTRs) and certain cellular genes in distant regions, induces cells to produce IL-2 and IL-2R, and stimulates infected CD4 T cells. It causes it to proliferate and divide, reaching an uncontrollable level and then developing leukemia.

HTLV-I/II virus-infected patients may have specific antibodies against various viral polypeptides. Most of the antibodies are not protective, and the antibodies against env antigen have a certain neutralizing effect, but the protection is weak, in vitro experiments. It is suggested that cellular immunity may play an important role in fighting tumors and killing HTLV-I.

Human T lymphocyte virus infection prevention

Should avoid sharing needles, syringes; surgical, acupuncture and other equipment to pay attention to disinfection; do not use unsterilized instruments to wear ears, eyebrows.

To strengthen non-flowable blood supply and blood supply, it is necessary to receive law-abiding education such as HIV antibody testing. Blood donors should be tested for HTLV and positive candidates should be excluded.

HTLV-positive mothers should avoid breastfeeding; ask a doctor during pregnancy to prepare and treat accordingly.

Use condoms correctly in your sexual life. Patients pay special attention to prevent transmission to sexual partners, establish correct sexual attitudes, and cleanse themselves.

Human T lymphocyte virus infection complications Complications portal hypertension ascites pleural effusion

Concurrent portal hypertension, ascites, pleural effusion and so on.

Symptoms of human T lymphocyte virus infection Common symptoms Inability to mucosal damage Portal hypertensive meningeal irritation Ascites hepatosplenomegaly spinal cord lesions

The incubation period of this disease is uncertain. The elderly may take several years to several decades after the infection of HTLV to develop clinical symptoms. Recently, more HTLV-related diseases have been found.

1. Health with virus status

HTLV-I antibodies can be detected in adult T-cell leukemia/lymphoma (ATL) high-incidence areas, and HTLV can be isolated from HTLV-I antibody-positive lymphocyte cultures by 95% to 98%. HTLV carriers develop from these carriers to ALT about 1/103 per year.

2. Adult T cell leukemia/lymphoma (ATL, formerly known as ATLL)

Mainly caused by HTLV-I, according to clinical manifestations, Shimoyama divided it into 4 subtypes.

(1) Smouldering ATL: It is characterized by abnormal T cells accounting for 5% or more of the total number of normal lymphocytes in the peripheral blood, accompanied by skin damage, even involving the lungs, but no hypercalcemia Symptoms, lymphadenopathy or visceral damage, serum LDH levels may increase, this type of progress is slow, often can last for several years.

(2) Chronic ATL: characterized by an increase in the absolute number of lymphocytes (4 × 10 ⁹ /L or more), accompanied by T lymphocytosis (more than 3.5 × 10 ⁹ / L), serum LDH increased to 2 times the normal value, There are lymphadenopathy, hepatosplenomegaly, skin and lung damage, no hypercalcemia, ascites and pleural effusion, or central nervous system, bone or gastrointestinal damage, this type of patient The average survival time is 24 months.

(3) Lymphoma ATL: Lymph node disease without lymphocytosis, which must be confirmed by histopathology as a lymphoma. This type survives on average for about 10 months.

(4) Acute ATL: Including some patients with high-grade non-Hodgkin's lymphoma with leukemia or with leukemia cells in the blood, hypercalcemia, lytic bone damage and visceral damage are common. Can be converted from any stage of insidious or chronic disease to acute, prognosis

Poor, the average survival time is only 6.2 months.

3.T hairy cells / giant cell leukemia

Related to HTLV-II, it is common to have fever, anemia and splenomegaly. It is accompanied by hypersplenism, portal hypertension and ascites. Peripheral blood and bone marrow can find hairy cells and have high levels of TNF-. Wait.

4. Central nervous system damage

More common in 40 to 50 years old HTLV-I infection, can show symptoms of pia mater, such as meningeal irritation, mental changes, etc.; spinal cord lesions, limb weakness, numbness or loss of the toe and lower extremity tonic spasm.

Examination of human T lymphocyte virus infection

Laboratory examination is an important basis for the diagnosis of HTLV infection, mainly in the following aspects.

Cytological examination

Can be used for peripheral blood or bone marrow cytology. The diagnosis of adult T-cell leukemia/lymphoma is based on the discovery of abnormal leukemia cells, ie, medium-sized abnormal lymphocytes with less cytoplasm, no particles, and sometimes vacuoles. Acute ALT can be seen with irregular nuclei, multi-shape changes, distorted deformities or lobulated, called flower cells; chronic forms of typical cleaved cells; insidious types can also be seen characteristic Cell morphology (Figure 2).

Cytochemical staining: glycogen staining was positive, acid phosphatase was weakly positive or negative.

A and B: acute multi-leaf morphology B can be seen in flower cell C: chronic type, typical cleft cells are seen. D: typical cell morphology of invasive ALT (smoulding ALT).

2. Serum HTLV-I/II antibody detection

Indirect immunofluorescence (IFA) gelatin particle agglutination (GPA), radioimmunoassay (RIA) enzyme-linked immunosorbent assay (ELISA) and Western blotting (WB) are currently used. The antigen is commonly used in HTLV-infected cell line lysates, purified virions or polypeptide-synthesized polypeptides or recombinant polypeptides, among which ELISA is currently the most commonly used detection method.

3. HTLV virus particles and their antigen detection

Peripheral lymphocytes isolated from fresh blood of ATL patients or HTLV carriers were treated and cultured in a 37 ° C 5% carbon dioxide incubator for 3 to 6 weeks. The virus particles of the cells were observed by electron microscopy or the cells on the cell surface were examined by immunofluorescence. antigen.

4. HTLV PCR detection

A common primer and probe for designing HTLV-I and HTLV-II in a conserved region of the gag, pol, and env genes of HTLV were selected for PCR reaction.

5. Cerebrospinal fluid examination

For patients with central nervous system symptoms, cerebrospinal fluid examination may be taken. Generally, the protein content is high, up to 2.1g/L, and the level of gamma globulin is high. There are high titers of HTLV antibodies and lymphocytes and ALT-like cells.

Diagnosis and identification of human T lymphocyte virus infection

Adults with mature T-cell lymphoma, hypercalcemia and/or mucosal damage, especially in patients at high risk of HTLV or endemic areas should consider ATL diagnosis based on serum HTLV- I antibody positive, HTLV-I provirus (proviru s) found in blood or biopsy leukocytes.

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