HSV-1 vs HSV-2: Key Clinical Differences
HSV-1 primarily causes orolabial disease and is acquired through non-sexual contact (often in childhood), while HSV-2 predominantly causes genital disease with much higher recurrence rates and is sexually transmitted. 1
Anatomical Distribution
HSV-1 traditionally manifests above the neck (orolabial region), while HSV-2 typically affects areas below the waist (genital region), though this distinction has become less absolute due to oro-genital sexual practices 1
HSV-1 is commonly acquired through direct contact with infected saliva or lesions, typically during childhood 1, 2
HSV-2 is almost exclusively associated with genital disease and carries more social stigma, whereas HSV-1 is associated with both oropharyngeal and genital disease 1
Epidemiology and Prevalence
HSV-1 has significantly higher prevalence: approximately 47.8% of the US population aged 14-49 years 1
HSV-2 prevalence is lower: 12.1% in the same US population 1
HSV-1 seroprevalence increases progressively from childhood and is inversely related to socioeconomic background 2
Clinical Manifestations
Primary Infection
Primary HSV-1 gingivostomatitis presents with fever, irritability, tender submandibular lymphadenopathy, and painful oral/perioral ulcers affecting the tongue, lips, gingiva, buccal mucosa, and hard/soft palate 1, 2
Primary genital herpes (typically HSV-2) presents with lesion evolution from papule to vesicle to ulcer to crust, accompanied by pain, pruritus, dysuria, vaginal/urethral discharge, and inguinal lymphadenopathy 1
The incubation period for both viruses is 2-10 days, up to 4 weeks 1
Primary infection is typically the most severe manifestation for both virus types 1
Recurrent Infection
HSV-2 recurs much more frequently in the genital area than HSV-1, with a significantly higher monthly recurrence frequency 1, 3
Genital HSV-2 infections recur at a mean rate of 0.33 per month, compared to only 0.020 per month for genital HSV-1 infections 3
Oral-labial HSV-1 infections recur at 0.12 per month, while oral HSV-2 infections recur at only 0.001 per month 3
Genital HSV-1 infections have a more benign natural history with fewer recurrences compared to genital HSV-2, which is critical information for patient counseling 1
Most genital herpes cases (80-90%) progress subclinically but may become symptomatic at any time 1
Latency and Neurotropism
HSV-1 establishes latency in the trigeminal ganglia, while HSV-2 establishes latency in the sacral ganglia 1
Both viruses remain in a non-multiplying episomal form in neural ganglia during latency periods, resulting in lifelong infection 1
Changing Epidemiological Patterns
HSV-1 is increasingly causing genital herpes: 20-25% of genital herpes cases in developed countries are now caused by HSV-1 4, 5
This shift is attributed to changing sexual practices (oro-genital contact) and delayed acquisition of HSV-1 from childhood to adolescence/adulthood in developed countries 4, 6
Mixed HSV-1/HSV-2 genital infections occur in approximately 27% of cases 5
Clinical Implications
Type-specific testing is essential because it predicts recurrence patterns and guides patient counseling about expected natural history 1
HSV-2 is a risk factor for HIV acquisition, and HSV-2 reactivation can increase HIV RNA levels in coinfected patients 1
Neonatal herpes and increased risk for acquiring HIV are the most serious complications of genital herpes infections 1
Antiviral Susceptibility
Both HSV-1 and HSV-2 are susceptible to acyclovir, valacyclovir, and famciclovir, which work through viral thymidine kinase phosphorylation 7, 8
The EC50 values for acyclovir range from 0.09-60 μM for HSV-1 and 0.04-44 μM for HSV-2 7
Resistance can develop through mutations in viral thymidine kinase or DNA polymerase genes, with cross-resistance observed among acyclovir, penciclovir, and famciclovir 7, 8