What are the characteristic differences between Herpes Simplex Virus 1 (HHV1) and Herpes Simplex Virus 2 (HHV2)?

Characteristic Differences Between HSV-1 (HHV1) and HSV-2 (HHV2)

HSV-1 (HHV1) primarily causes infections above the waist, particularly oral lesions, while HSV-2 (HHV2) predominantly causes infections below the waist, specifically genital lesions, though both viruses can infect either location depending on sexual practices. 1

Anatomical Distribution and Transmission

HSV-1 (HHV1)

• Typically manifests above the neck (orolabial region) 1
• Usually acquired through close non-sexual contact with infected persons, commonly in childhood 1
• Primarily affects the oro-pharynx, mouth, lips, and chin 1
• Can occasionally affect the eyes 1
• Can cause genital herpes through oro-genital sexual practices 1, 2
• Responsible for 98.4% of oral lesions according to one urban population study 2

HSV-2 (HHV2)

• Typically manifests below the waist (genital region) 1
• Usually acquired through sexual contact later in life 1
• Primarily affects genital mucosa, genital skin, and perigenital region 1
• Responsible for 83.6% of genital lesions according to one urban population study 2
• Can occasionally cause oral infections through oro-genital contact 3

Clinical Manifestations

HSV-1 (HHV1)

• Orolabial herpes is the most common manifestation 1
• Classic presentation includes sensory prodrome followed by papules, vesicles, ulcers, and crusts on the lips 1
• Lesions typically last 7-10 days if untreated 1
• Recurs 1-12 times per year 1
• Can be triggered by sunlight or physiologic stress 1
• When causing genital infection, recurs less frequently than HSV-2 1

HSV-2 (HHV2)

• Genital herpes is the most common manifestation 1
• Similar appearance and evolution to orolabial lesions 1
• Often accompanied by dysuria, vaginal/urethral discharge, and inguinal lymphadenopathy (particularly in primary infection) 1
• Most infections (80-90%) progress subclinically 1
• Recurs more frequently in the genital area compared to HSV-1 1
• In immunocompromised patients with CD4+ counts <100 cells/μL, can cause extensive, deep, non-healing ulcerations 1

Latency and Recurrence

HSV-1 (HHV1)

• Establishes latency in the trigeminal ganglia 3
• Recurrent infections typically affect the same site as the primary infection 1

HSV-2 (HHV2)

• Establishes latency in the sacral ganglia 3
• Recurrences arise with variable frequency, from once every few years to several times per month 1

Incubation and Disease Course

Both HSV-1 and HSV-2

• Incubation period is typically 2-10 days (up to 4 weeks) 1
• Primary infection is usually the most severe manifestation 1
• Both cause life-long infections 1
• Both can cause severe disease in immunocompromised hosts 1
• Recurrent episodes typically last less than 10 days but may be prolonged due to secondary bacterial infection or immunosuppression 1

Genetic Diversity

HSV-1 (HHV1)

• Shows greater glycoprotein sequence diversity compared to HSV-2 4

HSV-2 (HHV2)

• Shows less glycoprotein sequence diversity but several HSV-2 glycoproteins evolve under less selective pressure 4
• Some African strains show unique amino acid signatures in glycoproteins G, I, and E, which can affect diagnostic test accuracy 4

Epidemiology and Cross-Protection

• Previous HSV-1 infection does not reduce the rate of HSV-2 acquisition 5
• However, prior HSV-1 infection increases the likelihood of asymptomatic HSV-2 seroconversion by a factor of 2.6 5
• When a person with antibodies to HSV-1 acquires HSV-2, the genital infection is typically less severe but still associated with recurrences 1

Diagnostic Considerations

• Laboratory confirmation is essential for accurate diagnosis, especially in HIV-positive patients 1
• Typing of the virus detected in genital lesions is important as HSV-1 recurs less frequently than HSV-2 in the genital area 1
• Preferred diagnostic methods include viral culture, HSV DNA PCR, and HSV antigen detection 1
• PCR is the most sensitive method but not widely available 1

Clinical Pitfalls to Avoid

• Do not rely solely on anatomical location for differentiating HSV-1 from HSV-2, as either virus can infect either location 1
• Do not assume all genital herpes is caused by HSV-2; HSV-1 is increasingly common as a cause of genital herpes 1, 6
• Do not diagnose HSV infections without laboratory confirmation, especially in atypical presentations or immunocompromised patients 1
• Be aware that mixed infections with both HSV-1 and HSV-2 can occur simultaneously, with different ratios of viral genomes depending on the infection site 3