What are the main differences between Herpes Simplex Virus (HSV) 1 and Herpes Simplex Virus (HSV) 2?

Main Differences Between HSV-1 and HSV-2

HSV-1 and HSV-2 differ primarily in their anatomical site preferences, recurrence patterns, and epidemiological characteristics, though both can infect either oral or genital regions.

Anatomical Distribution and Site Preference

• HSV-1 traditionally causes orolabial disease (above the neck), while HSV-2 typically causes genital infections (below the waist), though this distinction has become less absolute due to changing sexual practices 1
• HSV-1 establishes latency in the trigeminal ganglia, whereas HSV-2 resides in the sacral ganglia 1
• In mixed infection cases, the genome ratio reflects each virus type's organ preference: HSV-1 dominates in ocular infections at approximately 100:1 ratio, while HSV-2 predominates in genital infections at 4-40 times higher frequency 2

Epidemiology and Prevalence

• HSV-1 has substantially higher prevalence at 47.8% of the US population aged 14-49 years, compared to HSV-2 at 12.1% 1
• Among sexually active adults, new HSV-2 infections occur at a rate of 5.1 cases per 100 person-years, compared to 1.6 cases per 100 person-years for HSV-1 3
• Women are more likely than men to acquire HSV-2 infection 3

Recurrence Patterns

• HSV-2 recurs much more frequently in the genital area than HSV-1, with significantly higher monthly recurrence rates 1
• This difference in recurrence frequency is clinically important for counseling patients and predicting disease course 1

Clinical Manifestations

Primary Infection

• Both viruses cause similar clinical presentations during primary infection, with vesicles progressing through papule, vesicle, ulcer, and crust stages 1
• Primary HSV-1 gingivostomatitis presents with fever, irritability, tender submandibular lymphadenopathy, and painful oral/perioral ulcers 4
• Primary genital herpes (typically HSV-2) presents with local symptoms including pain, pruritus, dysuria, vaginal/urethral discharge, and inguinal lymphadenopathy 1
• Approximately 37% of new HSV-2 infections are symptomatic, while nearly two-thirds of new HSV-1 infections present with symptoms 3

Asymptomatic Shedding

• Most genital herpes cases (80-90%) progress subclinically but may become symptomatic at any time 1
• Previous HSV-1 infection does not reduce the rate of HSV-2 acquisition but increases the likelihood of asymptomatic HSV-2 seroconversion by a factor of 2.6 3

Changing Epidemiological Patterns

• Among sexually active adults, new genital HSV-1 infections are now as common as new oropharyngeal HSV-1 infections (0.5 cases per 100 person-years for each) 3
• In developed countries, delayed acquisition of HSV-1 from childhood to adolescence/adulthood partially explains the increase in genital herpes caused by HSV-1 5

Clinical Implications

HIV Interaction

• HSV-2 is a significant risk factor for HIV acquisition, and HSV-2 reactivation can increase HIV RNA levels in coinfected patients 1
• This interaction is particularly important in regions with high prevalence of both infections 5

Diagnostic Considerations

• Type-specific serologic testing is essential because HSV type determination helps predict recurrence patterns and guides patient counseling 1
• Clinical diagnosis alone has a true positive to false positive ratio of 4:1, emphasizing the need for laboratory confirmation 3

Treatment Response

• Both viruses respond to the same antiviral agents (acyclovir, valacyclovir, famciclovir), which act through inhibition of viral DNA polymerase 6, 7
• The antiviral activity differs slightly: acyclovir EC50 values range from 0.09-60 μM for HSV-1 and 0.04-44 μM for HSV-2 6

Common Pitfalls

• Do not assume anatomical site reliably predicts HSV type—both viruses can infect either oral or genital regions 1, 2
• Do not rely solely on clinical appearance to differentiate HSV-1 from HSV-2, as they are visually indistinguishable 8
• Do not assume prior HSV-1 infection provides protection against HSV-2 acquisition 3