Herpes simplex virus 1 (HSV‑1) is an enveloped double‑stranded DNA virus of the Alphaherpesvirinae subfamily that primarily causes oral herpes and establishes latent infection in sensory ganglia.
Biology and Pathogenesis
HSV‑1 has a linear double‑stranded DNA genome enclosed within an icosahedral capsid, surrounded by a tegument layer and a lipid envelope studded with viral glycoproteins. These glycoproteins mediate attachment and entry into host epithelial cells by binding receptors such as nectin‑1. After replication in epithelial tissues, the virus travels retrogradely along sensory axons to the trigeminal ganglion, where it establishes latency. During latency the genome persists as an episome with minimal gene expression; periodic reactivation leads to anterograde transport of virions back to the skin or mucosa. Reactivation can be triggered by fever, stress, ultraviolet light or immunosuppression. HSV‑1 infections are usually acquired in childhood through saliva or close contact. Primary infection may present as gingivostomatitis with fever and painful ulcers, while many infections are asymptomatic. The virus can also cause keratitis, encephalitis and, less commonly, genital lesions. Diagnosis is based on clinical appearance supported by PCR or culture. Nucleoside analogues such as acyclovir, valacyclovir or famciclovir reduce viral replication but do not eradicate latency. No vaccine is currently available.
Clinical Manifestations and Epidemiology
The most recognizable manifestation of HSV‑1 is the recurrent “cold sore” on the lips or perioral skin. Orolabial reactivation often begins with prodromal tingling followed by vesicles that crust over within a week. Herpetic whitlow occurs when the virus infects fingers, typically in healthcare workers or children sucking their thumbs. HSV‑1 is the leading cause of infectious blindness in developed countries due to recurrent keratitis. It is also a significant cause of sporadic fatal encephalitis, presenting with fever, altered consciousness and temporal lobe involvement. Although HSV‑1 traditionally causes oral lesions and HSV‑2 causes genital herpes, increasing numbers of genital infections are due to HSV‑1 as a result of oral‑genital contact. Seroprevalence increases with age and is higher in regions with crowded living conditions. Transmission is reduced by avoiding contact during active lesions and by prophylactic antivirals in high‑risk individuals. Although HSV‑1 is widespread and establishes lifelong latency, most infections remain mild. Understanding its biology and triggers for reactivation helps manage symptoms and prevent transmission. Related Terms: herpes simplex virus 2, varicella‑zoster virus, latency, acyclovir, trigeminal ganglion