Herpes simplex virus type 1 (HSV-1) is a neurotropic virus that establishes latent infection in the trigeminal ganglia following primary infection. Its reactivation can be triggered by both internal and external factors, including heat stress, emotional stress, excessive consumption of warm-natured foods, and the administration of tonic and warming traditional Chinese medicines (TCMs). The fire-heat symptoms in the upper facial region induced by HSV-1 reactivation are consistent with the "Shanghuo" syndrome described in TCM. In this study, HSV-1 infection models established by corneal scarification and intranasal inoculation were systematically compared. Dynamic changes throughout the entire "primary infection-latency-reactivation" cycle were monitored using multiple parameters, including mortality, body weight, ocular manifestations, viral glycoprotein B (gB) mRNA expression, and restless behavior. This study aimed to provide a basis for model selection in investigating the biological mechanisms underlying TCM "Shanghuo" and for screening anti-HSV-1 therapeutics. The results showed that during the primary infection phase (0-14 d), mice in both groups exhibited body weight loss and ocular surface inflammation, with an earlier onset (3 d vs 5 d) and more severe ocular damage observed in the corneal scarification group. During the latency phase (28 days post-infection), latency-associated transcript (LAT) was detected in the trigeminal ganglia in both groups, with a higher latency rate in the corneal scarification group (100% vs 87.5%). Following heat stress-induced reactivation, the intranasal inoculation group exhibited a significantly higher reactivation rate (85.7% vs 66.6%), more pronounced restless behavior, and elevated levels of gB mRNA expression and viral titers in brain tissue compared with the corneal scarification group. In conclusion, both corneal scarification and intranasal inoculation successfully establish HSV-1 models encompassing the full cycle of primary infection, latency, and reactivation. Dynamic monitoring of infection stages can be achieved by detecting gB mRNA in eye wash fluid. The corneal scarification model, characterized by a high latency rate and prominent ocular manifestations, is suitable for studies of viral keratitis and related therapeutic evaluation. In contrast, the intranasal inoculation model, with a higher reactivation rate and marked restless behavior, exhibits similarities to the restless manifestations of the TCM "Shanghuo" heat pattern, suggesting its potential utility in evaluating the efficacy of heat-clearing TCMs. Animal experiments conducted in this study were approved by the Ethics Committee of Jinan University (approval No. IACUC-20260311-06).
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |