Molluscum Contagiosum Associated with Acquired Immunodeficiency Syndrome: Experience in HIV outpatient care and literature review / Molusco contagioso associado à síndrome da imunodeficiência adquirida: experiência no atendimento em ambulatório de HIV e revisão da literatura

Introduction: Molluscum contagiosum is a dermatosis caused by a DNA virus of the family Poxvirus and genus Molluscipoxvirus, affecting mainly children, sexually active adults, atopic individuals and immunocompromised patients, especially those with human immunodeficiency virus (HIV) infection. Objective: To describe our experience in caring for patients living with HIV who presented with extensive and severe Molluscum contagiosum, and to conduct a literature review on the subject as well. Methods: An electronic search was carried out in the MEDLINE/PubMed and SciELO databases and in the books: ATLAIDS and AZULAY limited to the period of January 2017 to June 2021. Results: Four clinical cases are reported in people living with HIV with extensive lesions normally not found in immunocompetent patients. The treatment performed in the cases reported in this article was the punctual application of 90% trichloroacetic acid (TCA) to each lesion, with complete remission of the clinical presentation in two patients over a period of three and six months. The other two patients did not receive treatment for molluscum contagiosum as they died because of pulmonary complications. Conclusion: Infection with Molluscum contagiosum in people living with HIV has disseminated forms with large-volume lesions, with substantial stigmatizing aesthetic impairment, and treatment with 100% TCA is quite effective.

Introdução: Molusco contagioso é uma dermatose causada por um vírus de DNA da família poxvírus e do gênero Molluscipoxvirus. Afeta principalmente crianças, adultos sexualmente ativos, indivíduos atópicos e pacientes imunodeprimidos, especialmente aqueles com infecção pelo vírus da imunodeficiência humana (HIV). Objetivo: Descrever a experiência no atendimento de pacientes vivendo com HIV que apresentaram quadro de molusco contagioso extenso e grave, além de realizar uma revisão da literatura sobre o tema. Métodos: Foi realizada uma pesquisa eletrônica nas bases de dados MEDLINE/PubMed e SciELO e nos livros ATLAIDS e AZULAY, limitada ao período de janeiro de 2017 a junho de 2021. Resultados: São relatados quatro casos clínicos em pessoas que vivem com HIV com lesões extensas normalmente não encontradas em pacientes imunocompetentes O tratamento realizado nos casos relatados nesse artigo foi a aplicação pontual de ácido tricloroacético (ATC) 100% em cada lesão, com a remissão completa do quadro clínico em dois pacientes em um período de tempo entre três e seis meses. Os outros dois pacientes não receberam tratamento para o vírus do molusco contagioso pois evoluíram para óbito em razão de complicações pulmonares. Conclusão: A infecção pelo molusco contagioso em pessoas vivendo com HIV apresenta formas disseminadas com lesões de grande volume, com comprometimento estético estigmatizante importante, e o tratamento com ATC 90% é bastante eficaz.

Molecular and genomic characterization of a novel equine molluscum contagiosum-like virus.

Cases of pox-like lesions in horses and donkeys have been associated with poxviruses belonging to different genera of the family Poxviridae. These include the orthopoxviruses vaccinia virus (VACV), horsepoxvirus (HPXV) and cowpoxvirus (CPXV), as well as a potentially novel parapoxvirus and molluscum contagiosum virus (MOCV). However, with the exception of VACV, HPXV and CPXV, the genomic characterization of the causative agents remains largely elusive with only single short genome fragments available. Here we present the first full-length genome sequence of an equine molluscum contagiosum-like virus (EMCLV) directly determined from skin biopsies of a horse with generalized papular dermatitis. Histopathological analysis of the lesions revealed severe epidermal hyperplasia with numerous eosinophilic inclusion bodies within keratinocytes. Virions were detected in the lesions in embedded tissue by transmission electron microscopy. The genome sequence determined by next- and third-generation sequencing comprises 166 843 nt with inverted terminal repeats (ITRs) of 3473 nt. Overall, 20 of the predicted 159 ORFs have no equivalents in other poxviruses. Intriguingly, two of these ORFs were identified to encode homologues of mammalian proteins involved in immune signalling pathways, namely secreted and transmembrane protein 1 (SECTM1) and insulin growth factor-like family receptor 1 (IGFLR1), that were not described in any virus family so far. Phylogenetic analysis with all relevant representatives of the Poxviridae suggests that EMCLV should be nominated as a new species within the genus Molluscipoxvirus.

Poxviruses Utilize Multiple Strategies to Inhibit Apoptosis.

Cells have multiple means to induce apoptosis in response to viral infection. Poxviruses must prevent activation of cellular apoptosis to ensure successful replication. These viruses devote a substantial portion of their genome to immune evasion. Many of these immune evasion products expressed during infection antagonize cellular apoptotic pathways. Poxvirus products target multiple points in both the extrinsic and intrinsic apoptotic pathways, thereby mitigating apoptosis during infection. Interestingly, recent evidence indicates that poxviruses also hijack cellular means of eliminating apoptotic bodies as a means to spread cell to cell through a process called apoptotic mimicry. Poxviruses are the causative agent of many human and veterinary diseases. Further, there is substantial interest in developing these viruses as vectors for a variety of uses including vaccine delivery and as oncolytic viruses to treat certain human cancers. Therefore, an understanding of the molecular mechanisms through which poxviruses regulate the cellular apoptotic pathways remains a top research priority. In this review, we consider anti-apoptotic strategies of poxviruses focusing on three relevant poxvirus genera: Orthopoxvirus, Molluscipoxvirus, and Leporipoxvirus. All three genera express multiple products to inhibit both extrinsic and intrinsic apoptotic pathways with many of these products required for virulence.

Primitive follicular induction in molluscum contagiosum.

BACKGROUND: Molluscum contagiosum (MC) is the commonest human poxvirus infection. Follicular induction has rarely been observed in the epidermis surrounding lesions of MC. A virus-induced localized proliferation of germinative/stem cells of the folliculosebaceous-apocrine unit has been suggested as the underlying cause, however few reports of this peculiar phenomenon exist in the literature and the mechanisms involved in this proliferation require further study. METHODS: We prospectively collected MC cases showing multifocal areas of primitive follicular induction involving the adjacent undersurface epidermis. Immunohistochemical expression of BerEP4, PHLDA1 and cytokeratin 20 (CK20) was evaluated in the basaloid germs surrounding the lesions. For PHLDA1, we used epidermal melanocytes as a positive internal control. For BerEP4, we employed a basal cell carcinoma (BCC) and for CK20, colon as positive external controls. An incubation without the primary antibody functioned as an external negative control. RESULTS: All the cases studied showed an intense positive staining of the basaloid buds with BerEP4 and weaker stain for PHLDA1. CK20 showed the presence of scattered Merkel cells within the induced epidermal basaloid proliferations favoring their reactive origin. DISCUSSION: The pathogenetic mechanisms behind the development of these microscopic features and the link between follicular induction and poxvirus infection are explored. Awareness of this unusual phenomenon by dermatopathologists will be helpful in avoiding a misdiagnosis of a superficial BCC in such cases. CONCLUSIONS: BerEP4 and PHLDA1 were consistently expressed in the areas of primitive follicular induction surrounding lesions of MC. CK 20 stained the Merkel cells present in the basaloid buds. All these findings support the reactive origin of this phenomenon, which we believe is most probably viral-induced.

The TRAF3-binding site of human molluscipox virus FLIP molecule MC159 is critical for its capacity to inhibit Fas-induced apoptosis.

Members of the viral Flice/caspase-8 inhibitory protein (v-FLIP) family prevent induction of apoptosis by death receptors through inhibition of the processing and activation of procaspase-8 and -10 at the level of the receptor-associated death-inducing signaling complex (DISC). Here, we have addressed the molecular function of the v-FLIP member MC159 of the human molluscum contagiosum virus. MC159 FLIP powerfully inhibited both caspase-dependent and caspase-independent cell death induced by Fas. The C-terminal region of MC159 bound TNF receptor-associated factor (TRAF)3, was necessary for optimal TRAF2 binding, and mediated the recruitment of both TRAFs into the Fas DISC. TRAF-binding-deficient mutants of MC159 showed impaired inhibition of FasL-induced caspase-8 processing and Fas internalization, and had reduced antiapoptotic activity. Our findings provide evidence that a MC159/TRAF2/TRAF3 complex regulates a new aspect of Fas signaling, and identify MC159 FLIP as a molecule that targets multiple features of Fas-induced cell death.

Molluscum contagiosum: recent advances in pathogenic mechanisms, and new therapies.

Two poxviruses, Molluscum contagiosum virus (MCV) and Variola virus are specific to humans. MCV is present worldwide and is directly passed by direct skin to skin contact to produce cutaneous and, rarely, mucosal lesions. It occurs predominantly in preadolescent children, sexually active adults, participants in sports with skin to skin contact, and in individuals with impaired cellular immunity. MCV characteristically proliferates within the follicular epithelium, and with routine fixation produces an area of retraction artifact separating layers 1 to 3 of CD34+ stromal cells that immediately surround the follicle from the surrounding dermis. This feature may be obscured when the lesions are inflamed, usually after rupture into the surrounding dermis. MCV is a cytoplasmically replicating virus. MCV-infected cells grow in size, while internal organelles are dislocated and eventually obliterated by a large intracytoplasmic inclusion. Rupture and discharge of the virus-packed cells occurs in a process similar to membrane debris and MCV accumulate in the crater-like ostium; MCV infection is spread by contact with infectious debris. In HIV-1-positive patients the histologic features, as well as the clinical features, may be atypical in patients with MCV infections. Not only are the lesions often large, but they may be verrucous and markedly hyperkeratotic. Recent sequencing of the MCV genome has increased our understanding and investigations into its mechanisms for avoiding host defense mechanisms. These include regions which encode for homologues of cellular chemokines and chemokine-binding proteins, a homolog of MHC1 and a viral FLICE-like inhibitory protein. Treatment, until recently, has depended upon tissue destruction including curettage, cryotherapy, CO(2) laser, electrodesiccation, trichloracetic acid and cantharadin. Recently, topical immune modulators have been used with some success. Understanding of the MCV genome is providing the basis for the development of drugs for therapy and prevention of MCV infections.

Transformación maligna de la enfermedad de Von Recklinghausen a propósito de un caso / Malignant changing of the Von Recklinghausen disease about a case

Presentamos este caso clínico como una malignización de la neurofibromatosis, hecho que según Hosoi estima que ocurre en un 13 por ciento de los casos de la enfermedad de Von Recklinghausen. Esta malignización puede ocurrir a cualquier edad siendo más común en personas de edad avanzada. Esta patología rara vez produce síntomas locales excepto aquellos debidos a su masa