Herpes simplex virus (HSV): can cause a variety of human diseases, such as gingivostomatitis, keratoconjunctivitis, encephalitis, and infections of the reproductive system and newborns. After infecting the host, latent infection is often established in nerve cells, and activation is followed by asymptomatic detoxification, maintaining the chain of transmission in the population in a circumferential cycle.
Definition
Herpes simplex is a viral skin disease caused by the herpes simplex virus, known in Chinese medicine as fever sores. Herpes simplex belongs to the a-virus subfamily of the herpesviridae family and has a viral plasmid size of approximately 180 nm. The virus is currently classified into type 1 and type 2 based on differences in antigenicity. type 1 is mainly acquired from oral and lip lesions, while type 2 can be isolated from genital lesions. The infection is due to human-to-human contact. The number of people infected from four months to several years after its occurrence can reach 50-90% of the total population. It is one of the most aggressive viruses in humans, but only a fraction of them develop clinically. The disease can be divided into: oral-labial herpes, herpetic keratitis, herpetic dermatitis, herpes pubis, Kaposi’s disease, etc. It is sometimes the cause of meningitis and encephalitis. Oral and labial herpes is generally easier to diagnose, while recurrence is caused by various irritants such as sunlight and fever. The virus can proliferate in large numbers on the chorionic villi allantoic membrane of chicken embryos and in animal culture cells of humans, monkeys, and chickens. In addition, the type 2 virus has a transforming effect on vole cells and others. Herpes viruses are also suspected to be associated with cervical cancer in humans.
Biological traits
HSV has typical herpesvirus morphological characteristics. It is classified into two serotypes, based on biochemistry, biology, and epidemiology
HSV-1 and HSV-2, which have similar genomes and 50% sequence homology, are distinguished by DNA restriction endonuclease analysis. the HSV genome is approximately 152 kb, with 34 genes encoding more than 70 polypeptides. In particular, the ? genes encode 11 envelope glycoproteins (gB, gC, gD, gE, gG, gH, gI, gJ, gK, gL, gM) among the late proteins, some of which are more clearly functional. Among them, gB and gD are associated with virus adsorption and penetration, and are viral ligand molecules that interact with cell-specific receptors. gD has the strongest ability to induce neutralizing antibodies and can be used to develop vaccines. gC is a complement C3bD binding protein. gE is an Fc receptor that binds to the Fc end of IgG. gG is a type-specific antigen that distinguishes HSV-1 (gG-1) from HSV- gH is associated with the release of the virus.
HSV has a wide range of hosts for animal infections. HSV can proliferate in a variety of cells, and is commonly isolated from primary rabbit kidney, human embryonic kidney cells, and gopher kidney passaged cells. Infected cells soon show obvious cytopathic changes and eosinophilic intranuclear inclusion bodies.
Pathogenicity
Herpes simplex virus is widely distributed worldwide and infection is extremely common in the population, with a high number of latent and recurrent infections. Patients and carriers are the infectious agents of the disease. The virus can enter the body through direct contact with skin and mucous membranes or through sexual contact.
Typical histopathological changes are ballooning of infected cells, formation of intranuclear inclusion bodies and multinucleated giant cells.
Herpes simplex virus infects neonates, children and adults and is usually classified as a primary infection or a recurrent infection.
Primary infections
Primary infections with HSV-1 are usually confined to the oropharynx and are most common in gingivostomatitis. Clinical manifestations include clusters of herpes on the gums and cheeks, fever, sore throat, and ulcers upon rupture. It can also cause encephalitis and herpetic eczema of the skin. In adults, it can cause pharyngitis and tonsillitis. Primary infection with HSV-2 mainly causes genital herpes, which manifests as blistering ulcerative lesions on the penis in men and on the cervix, vulva, and vagina in women, with complications including extra-genital lesions and aseptic meningitis. The duration of disease is approximately 3 weeks. The virus is latent in the sacral ganglia.
Latent and recurrent infections
Latent infection of sensory neurons is a feature of neurotropic HSV and VZV. After primary infection with HSV in humans, HSV is often latent in the sensory ganglia for life and is sometimes detected in the vagus nerve, adrenal tissue, and brain. Approximately 1% of infected cells carry the viral gene, and the viral DNA exists as free cyclic appendages, with approximately 20 copies per infected cell. Only few viral genes are expressed in the latent state. When the body is exposed to various factors such as ultraviolet light (sun exposure), fever, trauma and emotional stress, bacterial or viral infections and the use of epinephrine, the latent virus is activated and the virus travels down the axons of sensory nerve fibers to the nerve endings and infects the epithelial cells, especially after bone marrow transplantation or high-dose chemotherapy, in the absence of prophylaxis, in about 80% of patients who relapse. Studies have shown that not all activation leads to significant damage, but can be asymptomatic detoxification. The mechanisms of latency and activation are not well understood. Viral RNA transcripts have been found in the nuclei of latently infected cells with HSV, but no virus-encoded protein has been confirmed and therefore escapes without being recognized by the immune system. Activation is associated with increased activity of CD8+ suppressor T cells, enhanced spread of the virus by certain factors such as prostaglandins, and decreased immune effector cell function; therefore, activation is associated with increased local prostaglandin levels and suppression of cellular immunity.
Neonatal and congenital infections
Neonatal herpes is a common and serious clinical infection, with a statistical mortality rate of more than 50% and severe injury in about 1/2 of those who survive. HSV-1 and HSV-2 can both infect newborns through the birth canal during delivery, with HSV-2 being the most common, accounting for about 75% of cases. It often occurs on the 6th day after birth.
The types of infection are.
1.Local injury of skin, eye and mouth ;
2. encephalitis;
3. The virus spreads to the internal organs and sepsis occurs, which often causes death.
Early anti-infection can reduce mortality. Caesarean section is an effective method to avoid reproductive tract infections. In pregnant women infected with HSV-1, the virus may infect the fetus via the placenta, causing miscarriage, stillbirth or congenital malformation.
Immunological
Primary infection with herpes simplex virus has the highest susceptibility in infants and children from 6 months to 3 years of age, and by adulthood about 70% to 90% of people have antibodies to HSV-1. Antibodies to HSV-2 gradually increase with sexual maturation. Neutralizing antibodies (IgM, IgG, IgA) appear in the blood about 1 week after the primary infection. Severe primary infections or frequent recurrent infections have increased antibody levels. These antibodies do not prevent recurrent infections or the recurrence of latent viruses, but they can reduce the severity of the disease.
Microbiological examination methods
Virus isolation and identification
Virus isolation and culture is a reliable basis for definitive clinical diagnosis of herpesvirus infection today. Skin can be collected.
HSV-1 structure
Specimens such as blister fluid, cerebrospinal fluid, corneal scrapings and saliva from genitalia and other lesions are inoculated with human diploid fibroblast cell line WI38 and other passaged cell lines such as Vero, BHK, etc. After 24 to 48 hours, the cells then show lesions such as swelling, rounding and cell fusion. The cells were then identified by immunofluorescent staining with monoclonal antibodies to HSV-1 and HSV-2 or by applying DNA restriction endonuclease profiling to determine the type.
Antibody detection
Commonly used methods for antibody detection include complement binding test, neutralization test, immunofluorescence and enzyme-linked immunosorbent assay, which are mostly used clinically for acute infection diagnosis and detection of organ transplant patients, as well as epidemiological investigation. If used for the diagnosis of acute infection, a double copy of serum should be taken in the acute and recovery periods, and IgG and IgM should be detected in the serum at the same time.
DNA testing
Lesion tissue or cells are taken, viral DNA is extracted, and hybridization with a labeled HSV DNA probe or PCR is applied to detect the gB glycoprotein gene of HSV-1 or HSV-2 to determine if the infection is HSV. This method has been used for the diagnosis of patients with suspected HSV encephalitis.
Principles of prevention and treatment
Currently, there are no specific and effective measures for the control of herpesvirus infection. Hope is placed on the research of vaccines, especially new vaccines such as subunit vaccines, recombinant live vaccines, and DNA vaccines. Trials have proven that vaccines are useful in stopping primary infections, but recombinant HSV-2 glycoprotein vaccines, although they induce high levels of neutralizing antibodies, do not protect against genital reinfection.
Among the anti-HSV drugs, acyclic guanosine, propoxyphene, and adenosine are commonly used in clinical practice. IFN is also effective in herpetic keratitis.