What causes herpes simplex virus type 1 (HSV‑1) infection?

What Causes HSV-1 Infection?

HSV-1 infection is acquired through close contact with infected persons, typically during childhood via oral secretions, though increasingly through oro-genital sexual contact in adults causing genital infections. 1

Primary Transmission Routes

Oral Acquisition (Traditional Route)

• Direct contact with infected oral secretions is the classic transmission mechanism, usually occurring in childhood 1
• The virus spreads through close personal contact with someone actively shedding virus, even if they appear asymptomatic 1
• After primary infection at oral sites, HSV-1 establishes latency in the cervical ganglia, where it persists lifelong and can reactivate 1
• The incubation period ranges from 2 to 10 days (up to 4 weeks) after exposure 1

Genital Acquisition (Emerging Route)

• Oro-genital sexual practices have led to HSV-1 becoming an increasingly common cause of genital herpes 1
• In college student populations, HSV-1 now accounts for up to 78% of newly diagnosed genital herpes cases, representing a dramatic reversal from historical patterns 2
• This epidemiologic shift reflects declining childhood oral acquisition and increasing adult genital acquisition 3
• When acquired genitally, HSV-1 establishes latency in the sacral ganglia 1

Infection Mechanisms

Primary Infection

• Occurs when an HSV-seronegative person first acquires the virus 1
• Primary infection is typically the most severe manifestation, particularly in those without prior HSV-1 exposure 1
• Children may develop severe oro-pharyngitis following primary oral exposure 1
• Adults experiencing primary genital HSV-1 infection may develop severe genital lesions 1

Sites of Infection

• Above the neck: oro-pharynx, mouth, lips, chin, and occasionally eyes 1
• Below the waist: genital mucosa, genital skin (penile and labial), perigenital region 1
• Other sites: rectal mucosa, eyes, and potentially via hematogenous spread to multiple organs 1, 4

Important Clinical Considerations

Asymptomatic Transmission

• 80-90% of genital herpes cases progress subclinically, meaning most infected individuals transmit virus without knowing they are infected 1
• Asymptomatic viral shedding is a major driver of transmission 1

Recurrent Infections

• After primary infection resolves, the virus remains latent in sensory ganglia and can reactivate sporadically throughout life 1, 5
• Recurrences arise from viral reactivation, not new exposure, occurring with variable frequency from once every few years to several times monthly 1
• The site of recurrent lesions typically coincides with the primary infection site 1

Gender Differences

• Female mice demonstrate more effective HSV-1 colonization, particularly in gonads and brain, suggesting potential gender-dependent susceptibility differences 4
• HSV-1 genital infections are more common in females than males in college populations 2

Epidemiologic Trends

• HSV-1 seroprevalence in the U.S. is declining by 0.99-fold per year, reflecting reduced childhood oral acquisition 3
• Conversely, the proportion of HSV-1 detection in genital herpes is increasing by 1.02-fold per year 3
• Age remains a strong predictor, with seroprevalence increasing progressively from 38% in children to 63.5% in adults 3