**2.1 Clinical aspects of αHV lesions**

The transmission of αHV occurs by close contact with a person who actively eliminates the virus. The viral diffusion occurs from lesions; however, it can occur even if they are not visible. After the primary infection, the αHV remains quiescent in the nerve ganglia from which it can periodically reactivate, causing clinical manifestations. The HSV commonly cause a relapsing mucocutaneous infection affecting the skin, mouth, lips, eyes and genitals. Serious common variants include encephalitis, meningitis, neonatal herpes, and infections disseminated in immunosuppressed patients. There are two types of HSV: Herpes Simplex Virus 1 (HSV-1) and Herpes Simplex Virus 2 (HSV-2) and both types can cause oral or genital infections. In most cases, the HSV-1 causes gingivostomatitis, cold sores, herpetic keratitis, and lesions in the upper body. The HSV-2 generally causes lesions to the genitals and to the skin of the lower half of the body. Approximately 70% of population in USA is seropositive for HSV [3] but only the 20%, due to a decline in cellular immunity, presents the recurrent form that can occur with a variable frequency. The mucocutaneous manifestations occur in two forms: primary infection and recurrent infection. Both forms appear on the skin with an erythematous lesion with vesicles (the size of a pin's head) clustered that can merge to form a bubble and then break, leaving an erosion and then a crust that falls after a few days. The primary infection may be unapparent, so that most individuals carry antibodies but have no memory of the initial Herpes. In the forms where the disease manifests itself usually appears in children aged between 6 months and 3 years of age. It presents a clinical presentation often more serious than the classical that is shown in the recurrent form. In fact, it is associated with general malaise with temperature over 39°C, pain, dysphagia, sialorrhea, fetid breath. Despite the impressive appearance it resolves on its own in 10–15 days. During the primary infection the transmission of the virus is favored by alterations of the epithelial lining, so that it penetrates and multiplies in the epithelial cells, with lysis of the infected cells due to the formation of a large number of virions. The virus then disappears from the coating epithelium and goes, passing through the sensory nevi, to localize in the nerve ganglia corresponding to the entry area. In recurrent manifestations usually, after a prodromal period (typically <6 h in HSV-1 relapses) characterized by burning or pruritus, small vesicle bunches appear stretched on an erythematous base. The bunches are 0.5–1.5 cm in size but can flow together. Skin lesions of the nose, ears, eyes, fingers or genitals can be particularly painful. The vesicles normally persist for a few days, then break and dry, forming a thin yellowish crust. The lesions can be associated with a burning sensation, tingling or itching with or without fever and small adenopathies, the evolution lasts 1–2 weeks. The herpetic lesions typically heal completely, but recurrent lesions in the same site can cause atrophy and scarring. Skin lesions can develop bacterial superinfections. In patients with depression of cell-mediated immunity due to Human Immunodeficiency Virus infection (HIV) or other causes, long-lasting or progressive lesions may persist for weeks or longer. Herpes labialis (HL) occurs on the edge of the vermilion of the lip or, less frequently, on the mucosa of the hard palate. HL is the most common clinical form in the facial region [4]. In the United Kingdom it accounts for 1% of medical consultations [5]. The acute gingivostomatitis is characteristic of childhood. Instead, herpetic pharyngitides can occur in adults and children; occasionally, mediated by oro-genital contacts, caused by the HSV-2. The intraoral and gingival

**13**

*Sunlight and Herpes Virus*

**2.2 Pathogenesis**

*DOI: http://dx.doi.org/10.5772/intechopen.82643*

vesicles normally break in a time ranging from a few hours to 1–2 days, leaving an ulcer. Fever and pain often occur; after the resolution, the virus remains quiescent in the semilunar ganglion. The Genital Herpes (HG) is the most widespread sexually transmitted ulcerative disease in developed countries. HG can be caused by HSV-1 or HSV-2. Ocular HSV lesions (HO) can cause corneal scarring, and recurrent ocular HSV infections are a leading cause of vision loss [6]. VZV belongs to the αHV subfamily and produces two clinical syndromes: varicella (chickenpox) and zoster (shingles). Both "zoster" (from Greek) and "shingles" (from French and Latin languages) correspond to the English word "belt," which describes the characteristic narrow, bandlike rash from the spine to the front of the torso on one side of the body [7]. VZV is transmitted by inhalation of respiratory secretions or contact with skin lesions. During the primary infection (varicella), the virus becomes latent in the dorsal ganglia and zoster is due to reactivation from latency, a process which occurs most frequently in elderly [8]. Each person with a history of varicella has approxi-

HSV infections are most commonly acquired through direct contact with mucosal tissue or secretions of another infected person and the majority of infections are established within the stratified squamous epithelium of the skin and oral or genital mucosa [10]. The virus is able to cause a lytic infection with direct death of epithelial cells. Following infection, the virus enters sensory nerves that innervate the skin or mucosa and travels via retrograde axonal transport to the neuronal cell body: here it can establish a life-long latent infection in dorsal root ganglia [11]. In the cell body there is the nucleus, where the virus makes use of the cell's apparatus for DNA replication and transcription. The axonal cytoskeleton and molecular motors, like kinesins, are involved in the active transport of viral capsids and glycoproteins: their transport seems to be fast, bidirectional and microtubules dependent [12–14]. The mechanisms that regulate entry into lytic replication versus latent infection in neurons remain largely undefined. The mechanism of HSV entry is mediated by direct interaction between viral envelope glycoproteins and cell surface receptors that mediate attachment, initiate signaling cascades, or trigger virus internalization.

1.Attachment to the cell surface: the virus initially uses filopodial interaction to migrate toward the cell body and to initiate the access. This process is termed 'viral surfing' [15]. In this process, the initial binding of virus to cells is mediated through association of viral glycoprotein (g)B and/or gC with heparan sulfate proteoglycans (HSPG)s located on the cell surface, facilitating the subsequent binding to coreceptors. The gC makes the first contact with HSPGs on the cell surface, but in the absence of gC, gB can take over this function [16].

2.Binding to cell receptors and coreceptors: the major virus attachment is glycoprotein gD and the most studied coreceptor are nectin-1, herpes virus entry mediator or 3-O-sulfated HS. The interaction of the viral glycoproteins with these cell receptors induces conformational changes recruiting gB, gH, and gL for fusion of the viral envelope with the cell plasma membrane leading to viral penetration and capsid release in the cytoplasm [17]. The link between gD and

3.Fusion with cellular membrane: gH/gL provides the signal required for activation of gB. Binding of gB to one of its receptors, is required for

mately a 30% lifetime risk of at least one VZV reactivation [9].

The entry process involves multiple steps:

its receptor can activate the gH/gL complex.

#### *Sunlight and Herpes Virus DOI: http://dx.doi.org/10.5772/intechopen.82643*

vesicles normally break in a time ranging from a few hours to 1–2 days, leaving an ulcer. Fever and pain often occur; after the resolution, the virus remains quiescent in the semilunar ganglion. The Genital Herpes (HG) is the most widespread sexually transmitted ulcerative disease in developed countries. HG can be caused by HSV-1 or HSV-2. Ocular HSV lesions (HO) can cause corneal scarring, and recurrent ocular HSV infections are a leading cause of vision loss [6]. VZV belongs to the αHV subfamily and produces two clinical syndromes: varicella (chickenpox) and zoster (shingles). Both "zoster" (from Greek) and "shingles" (from French and Latin languages) correspond to the English word "belt," which describes the characteristic narrow, bandlike rash from the spine to the front of the torso on one side of the body [7]. VZV is transmitted by inhalation of respiratory secretions or contact with skin lesions. During the primary infection (varicella), the virus becomes latent in the dorsal ganglia and zoster is due to reactivation from latency, a process which occurs most frequently in elderly [8]. Each person with a history of varicella has approximately a 30% lifetime risk of at least one VZV reactivation [9].
