Cutaneous small-vessel vasculitis (CSVV) is a disorder characterized by neutrophilic inflammation predominantly limited to the superficial cutaneous postcapillary venules. CSVV may be idiopathic or may have a defined cause such as infection, medication, connective tissue disease, or malignancy. CSVV may also be associated with extracutaneous disease or systemic vasculitis. The most common clinical presentation of CSVV consists of symmetrically distributed palpable purpura of the lower extremities. In general, lesional skin biopsy samples should be examined with light microscopy and direct immunofluorescence for adult patients with suspected CSVV. A complete history, review of systems, physical examination, and selected laboratory studies also should be performed to assess for inciting causes or extracutaneous involvement of CSVV. Treatment varies and depends on the chronicity of CSVV, the severity of cutaneous involvement, and the presence or absence of both an underlying cause and extracutaneous involvement of CSVV. An isolated episode of CSVV associated with a known inciting factor may be managed by removal or treatment of the trigger, along with symptomatic measures. First-line systemic treatments for chronic, idiopathic CSVV include colchicine or dapsone, used singly or in combination. Recurrent, chronic, or severely symptomatic CSVV that does not respond to the aforementioned therapies may require initiation of an immunosuppressive agent such as azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, or rituximab.

Human papillomavirus type 16 (HPV16) has been identified as being the most common etiological agent leading to cervical cancer. Despite having a clear understanding of the role of HPV16 in oncogenesis, details of how HPV16 traffics during infection are poorly understood. HPV16 has been determined to enter via clathrin-mediated endocytosis, but the subsequent steps of HPV16 infection remain unclear. There is emerging evidence that several viruses take advantage of cross talk between routes of endocytosis. Specifically, JCV and bovine papillomavirus type 1 have been shown to enter cells by clathrin-dependent endocytosis and then require caveolin-1-mediated trafficking for infection. In this paper, we show that HPV16 is dependent on caveolin-1 after clathrin-mediated endocytosis. We provide evidence for the first time that HPV16 infection is dependent on trafficking to the endoplasmic reticulum (ER). This novel trafficking may explain the requirement for the caveolar pathway in HPV16 infection because clathrin-mediated endocytosis typically does not lead to the ER. Our data indicate that the infectious route for HPV16 following clathrin-mediated entry is caveolin-1 and COPI dependent. An understanding of the steps involved in HPV16 sorting and trafficking opens up the possibility of developing novel approaches to interfere with HPV16 infection and reduce the burden of papillomavirus diseases including cervical cancer.

Viruses may infect cells through clathrin-dependent, caveolin-dependent, or clathrin-and caveolin-independent endocytosis. Bovine papillomavirus type 1 (BPV1) entry into cells has been shown to occur by clathrindependent endocytosis, a pathway that involves the formation of clathrin-coated pits and fusion to early endosomes. Recently, it has been demonstrated that the closely related JC virus can enter cells in clathrincoated vesicles and subsequently traffic to caveolae, the organelle where vesicles of the caveolin-dependent pathway deliver their cargo. In this study, we use immunofluorescence staining of BPV1 pseudovirions to show that BPV1 overlaps with the endosome marker EEA1 early during infection and later colocalizes with caveolin-1. We provide evidence through the colocalization of BPV1 with transferrin and cholera toxin B that BPVl trafficking may not be restricted to the clathrin-dependent pathway. Disrupting the entry of caveolar vesicles did not affect BPV1 infection; however, we show that blocking the caveolar pathway postentry results in a loss of BPV1 infection. These data indicate that BPV1 may enter by clathrin-mediated endocytosis and then utilize the caveolar pathway for infection, a pattern of trafficking that may explain the slow kinetics of BPV1 infection.

Events that lead to viral infections include the binding of the virus to the target cells, internalization of the virus into the cells, and the ability of the viral genome to be expressed. These steps are mediated by cellular and viral proteins and are temporally regulated. The papillomavirus capsid consists of two virally encoded capsid proteins, L1 and L2. Much is known about the role of the major capsid protein L1 compared to what is known of the role of the L2 protein. We identified the interaction of the L2 protein with SNARE protein syntaxin 18, which mediates the trafficking of vesicles and their cargo between the endoplasmic reticulum, the cis-Golgi compartment, and possibly the plasma membrane. Mutations of L2 residues 41 to 44 prevented the interaction of L2 protein with syntaxin 18 in cotransfection experiments and resulted in noninfectious pseudovirions. In this paper, we describe that syntaxin 18 colocalizes with infectious bovine papillomavirus type 1 (BPV1) pseudovirions during infection but does not colocalize with the noninfectious BPV1 pseudovirions made with an L2 mutant at residues 41 to 44. We show that an antibody against BPV1 L2 residues 36 to 49 (␣L2 36-49) binds to in vitro-generated BPV1 pseudoviral capsids and does not coimmunoprecipitate syntaxin 18-and BPV1 L2-transfected proteins. ␣L2 36-49 was able to partially or completely neutralize infection of BPV1 pseudovirions and genuine virions. These results support the dependence of syntaxin 18 during BPV1 infection and the ability to interfere with infection by targeting the L2-syntaxin 18 interaction and further define the infectious route of BPV1 mediated by the L2 protein.Papillomaviruses (PVs) induce a variety of lesions such as cutaneous or genital warts in humans and exophytic papillomas of cutaneous or mucosal epithelia in animals. Human PV (HPV) infection is the most common sexually transmitted disease in the United States (approximately 5.5 million cases per annum) (31), and specific HPV genotypes (high risk) are the etiologic agents of cervical carcinoma, a major killer of women worldwide (23,(37)(38)(39). Bovine PV (BPV) infection causes benign tumors, which can result in squamous cell carcinoma in the presence of environmental factors such as bracken (7).The PV capsids consist primarily of two virally encoded proteins, L1 and L2, at an estimated ratio of 30:1 (17, 49). The L1/L2 ratio suggests that there is one L2 at each of 12 capsid vertices (49). Each viral particle contains a single doublestranded circular DNA genome of about 8 kb bound by histone proteins (15, 24), and the virus is assembled in the nucleus of squamous epithelial cells into particles that are 52 to 55 nm in diameter (9).The expression of the viral L1 protein in the absence of other viral proteins results in the packaging of viral DNA at inefficient levels (5, 50). The addition of L2 to viral particle production increases DNA packaging into virions (28, 53) and contributes to the infectious process of the virus (2, 18). Antibodies to L2 have proven to be ...

Lyme disease is an Ixodes tick-borne illness that may arise from different species of the Borrelia spirochete and may be propagated in various hosts. Humans are considered dead-end hosts in this propagation cycle but may have a range of Lyme disease characteristics as a result of borrelial infection. Lyme disease has varied cutaneous manifestations, and the approach to diagnosis and treatment is based on the patient, the region, and suspected coinfection with another tick-borne illness. An understanding of the distribution of the Ixodes tick, its vectors, and the most likely dermatologic presentation based on these factors allows the dermatologist to make appropriate testing and treatment recommendations. Our aim is to simplify this approach for the treating practitioner.