Molluscum contagiosum virus infection Chen, Xiaoying, MD; Anstey, Alex V, Prof; Bugert, Joachim J, Dr
The Lancet infectious diseases,
10/2013, Letnik:
13, Številka:
10
Journal Article
Recenzirano
Summary Molluscum contagiosum virus is an important human skin pathogen: it can cause disfigurement and suffering in children, in adults it is less common and often sexually transmitted. Extensive ...and persistent skin infection with the virus can indicate underlying immunodeficiency. Traditional ablative therapies have not been compared directly with newer immune-modulating and specific antiviral therapies. Advances in research raise the prospect of new approaches to treatment informed by the biology of the virus; in human skin, the infection is localised in the epidermal layers, where it induces a typical, complex hyperproliferative lesion with an abundance of virus particles but a conspicuous absence of immune effectors. Functional studies of the viral genome have revealed effects on cellular pathways involved in the cell cycle, innate immunity, inflammation, and cell death. Extensive lesions caused by molluscum contagiosum can occur in patients with DOCK8 deficiency—a genetic disorder affecting migration of dendritic and specialised T cells in skin. Sudden disappearance of lesions is the consequence of a vigorous immune response in healthy people. Further study of the unique features of infection with molluscum contagiosum virus could give fundamental insight into the nature of skin immunity.
Viral skin infections often affect the sports community. The aim of this study was to assess the rates, location sites, and seasons of appearance of common viral cutaneous diseases in beach ...volleyball athletes in Greece. Five hundred and forty-nine beach volleyball athletes participated in this study. The average age was 28.4 years. The viral infections were herpes simplex (type 1), molluscum contagiosum and warts. The measured parameters included: gender, age, the season when athletes may be more susceptible to infections and the location of infection in the body. Practicing information such as the number of training years, number of weekly trainings, and average hours of daily training was also recorded. Incidence rates correlated in relation to age: (a) warts (
< 0.001), molluscum contagiosum (
< 0.001), and herpes simplex (
= 0.001); (b) years of training: warts (
< 0.001), molluscum contagiosum (
< 0.001), and herpes simplex (
= 0.004); (c) average hours of daily training: molluscum contagiosum (
= 0.006) and herpes simplex (
< 0.010). The skin is the largest organ, and the risk of infection should not be underestimated. Prevention, early detection, recognition, and treatment are related to health and athletic performance, but also to the risk of transmission.
Searching for a pox on the house of molluscum Heymann, Warren R.
Journal of the American Academy of Dermatology,
February 2024, 2024-Feb, 2024-02-00, 20240201, Letnik:
90, Številka:
2
Journal Article
The molluscum contagiosum virus (MCV) uses a variety of immune evasion strategies to antagonize host immune responses. Two MCV proteins, MC159 and MC160, contain tandem death effector domains (DEDs). ...They are reported to inhibit innate immune signaling events such as NF-κB and IRF3 activation, and apoptosis. The RxDL motif of MC159 is required for inhibition of both apoptosis and NF-κB activation. However, the role of the conserved RxDL motif in the MC160 DEDs remained unknown. To answer this question, we performed alanine mutations to neutralize the arginine and aspartate residues present in the MC160 RxDL in both DED1 and DED2. These mutations were further modeled against the structure of the MC159 protein. Surprisingly, the RxDL motif was not required for MC160′s ability to inhibit MAVS-induced IFNβ activation. Further, unlike previous results with the MC159 protein, mutations within the RxDL motif of MC160 had no effect on the ability of MC160 to dampen TNF-α-induced NF-κB activation. Molecular modeling predictions revealed no overall changes to the structure in the MC160 protein when the amino acids of both RxDL motifs were mutated to alanine (DED1 = R67A D69A; DED2 = R160A D162A). Taken together, our results demonstrate that the RxDL motifs present in the MC160 DEDs are not required for known functions of the viral protein.
Molluscum contagiosum virus is a poxvirus belonging to the Poxviridae family, which includes Orthopoxvirus, Parapoxvirus, Yantapoxvirus, Molluscipoxvirus, Smallpox virus, Cowpox virus and Monkeypox ...virus. MCV belongs to the genus Molluscipoxvirus and has a tropism for skin tissue. MCV infects keratinocytes and, after an incubation period of 2 weeks to 6 weeks, causes a breakdown of the skin barrier with the development of papules of variable size depending on the proper functioning of the immune response (both adaptive and acquired). MCV only infects humans and does not cause viraemia. MCV encodes for several inhibitory proteins responsible to circumvent the immune response through different signalling pathways. Individuals who can be infected with MCV are children, immunocompromised individuals such as organ transplant recipients and Human Immunodeficiency Virus (HIV)-infected individuals. Current treatments to manage MCV-induced lesions are different and include the use of immunomodulators, which, however, do not provide an effective response.
The human specific poxvirus molluscum contagiosum virus (MCV) produces skin lesions that can persist with minimal inflammation, suggesting that the virus has developed robust immune evasion ...strategies. However, investigations into the underlying mechanisms of MCV pathogenesis have been hindered by the lack of a model system to propagate the virus. Herein we demonstrate that MCV-encoded MC80 can disrupt MHC-I antigen presentation in human and mouse cells. MC80 shares moderate sequence-similarity with MHC-I and we find that it associates with components of the peptide-loading complex. Expression of MC80 results in ER-retention of host MHC-I and thereby reduced cell surface presentation. MC80 accomplishes this by engaging tapasin via its luminal domain, targeting it for ubiquitination and ER-associated degradation in a process dependent on the MC80 transmembrane region and cytoplasmic tail. Tapasin degradation is accompanied by a loss of TAP, which limits MHC-I access to cytosolic peptides. Our findings reveal a unique mechanism by which MCV undermines adaptive immune surveillance.
Molluscum contagiosum virus (MCV) is the causative agent of molluscum contagiosum (MC), the third most common viral skin infection in children, and one of the five most prevalent skin diseases ...worldwide. No FDA-approved treatments, vaccines, or commercially available rapid diagnostics for MCV are available. This review discusses several aspects of this medically important virus including: physical properties of MCV, MCV pathogenesis, MCV replication, and immune responses to MCV infection. Sequencing of the MCV genome revealed novel immune evasion molecules which are highlighted here. Special attention is given to the MCV MC159 and MC160 proteins. These proteins are FLIPs with homologs in gamma herpesviruses and in the cell. They are of great interest because each protein regulates apoptosis, NF-κB, and IRF3. However, the mechanism that each protein uses to impart its effects is different. It is important to elucidate how MCV inhibits immune responses; this knowledge contributes to our understanding of viral pathogenesis and also provides new insights into how the immune system neutralizes virus infections.
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