How to establish a guinea pig genital herpes model? -Animal modeling

  Introduction: Type 1 (HSV-1) and type 2 (HSV-2) herpes simplex virus (HSV) infections are the most common human infections. The herpes simplex virus usually causes self-limiting oral and genital vesicular ulcers and often recurs. However, HSV can also cause more serious diseases and weakened immune systems in newborns, and is a common cause of encephalitis. In addition, HSV-2 infection is an important risk factor for HIV infection. Preventive and therapeutic vaccines are needed because the first HSV infection will cause an acute primary disease, which can be maintained and activated by latent nerve infection to produce recurrent disease or recurrent virus. For acute and recurrent diseases and recurrent viral shedding, improved antiviral drugs are needed. The ultimate goal of HSV preventive vaccines is to completely prevent infection, but this goal is difficult to achieve. Therefore, a vaccine that limits the initial amount of HSV replication and prevents or minimizes the clinical severity of acute diseases is a reasonable goal. The therapeutic vaccine target is the target for HSV infected patients. It can not only reduce the frequency and severity of recurrent disease, but also prevent or reduce recurrent shedding during symptomatic and asymptomatic relapse, including.

  Mouse model: The most commonly used models for studying HSV are selfed and non-selfed mouse models. There are models of the brain, mouth and face, cornea, nose, skin, newborns and genitals. Mice are relatively inexpensive and are of great help in understanding the molecular biology of acute and persistent infections and reactivation events. The main advantage of the mouse model is the large number of available reagents that can be used to study immune and molecular biological responses. In addition, knockout and knock-in strains can be used to selectively assess gene activity and function. The result of genital infection is affected by the age of the mouse, the inbred line used, the size of the inoculum and the HSV line used. When using them, you need to consider these variables. HSV-2 genital infections often have fatal consequences and limit the effectiveness of these studies. In addition, vaginal infections in mice require the use of methoxyprogesterone to synchronize the estrus cycle. This increases sensitivity and reduces the immune response of the genitals to the HSV-2 vaccine. After vaginal inoculation, animals develop genital diseases with erythema and swelling, but compared with guinea pigs, animals have fewer individual lesions and are more difficult to score. Thymidine kinase deficiency (TK-) virus is non-lethal, although since most animals die from infection after infection, it is impossible to assess potential infection, recurrent disease or recurrent virus shedding. Please note that it can be related to Use with mice. model. In short, as an early screening tool for cheap drugs and vaccines, the mouse model is the most valuable tool. It can determine the local and systemic immune response to infection and determine the possible protective response.

  Rat model: A lethal genital cotton rat model has been developed. Four days after taking medroxyprogesterone, cotton rats will be infected with HSV-1 and HSV-2 in the vagina. This model is used to evaluate the gD vaccine used in clinical trials. The two doses of the vaccine were immunogenic, but failed to prevent HSV-2 disease and reduce the replication of HSV-2 in the genitals. However, compared with HSV-2 genital diseases, the vaccine can significantly reduce vaginal HSV-1 titer and increase resistance to HSV-1. This model has aroused some interest because the results of these findings are consistent with large clinical trials. However, it should be noted that the study on cotton rats only used the vaccine twice, while it was used three times in clinical trials.

  Non-human primate model: Another model for testing antiviral agents, vaccines and fungicides is the macaque vagina HSV-2 infection model. This model has the unique ability to study the interaction between HSV-2 infection and HIV. Similar to the mouse genital HSV model, the animals were pretreated with methoxesterone 4-5 weeks before the vaginal injection of high-dose HSV-2. In this model, the lesions seem to be less common, but then the animals are infected. In one study, only 10% of HSV-2 macaques had cervical inflammation and/or lesions. However, during the 2-year follow-up period, about 50% of the animals found HSV-2 shedding and recorded the infection. A similar finding was found in another study. In the first 7 days after vaccination, infectious virus and HSV-2 DNA are always detected in genital secretions, but there are clinical symptoms of infection (pathological changes or systemic effects). Genital swab HSV-2 DNA was detected 42 and 56 days after HSV-2 inoculation, and the persistent and spontaneous activation of the latent virus was also recorded. As seen in humans, HSV-2 infection also increases the frequency of vaginal SIV-RT infections. Guinea pig model: HSV-2 genital model Description: The main advantage of the HSV-2 genital guinea pig model is that infected animals will develop acute self-limited diseases that are easy to quantify. These animals have easily recognizable spontaneous clinical relapses. Ultraviolet rays can also cause recurrent lesions. In addition, infected animals, with or without lesions, showed repeated shedding. An important factor in guinea pig infection is to mimic human disease. Another advantage is that animals can assess the presence and number of acute and persistent neurological infections, which is different from what humans can assess.