Molluscum contagiosum virus (MCV) is the sole member of the
genus and the causative agent of molluscum contagiosum (MC), a common skin disease. Although it is an important and frequent human ...pathogen, its genetic landscape and evolutionary history remain largely unknown. In this study, ten novel complete MCV genome sequences of the two most common MCV genotypes were determined (five MCV1 and five MCV2 sequences) and analyzed together with all MCV complete genomes previously deposited in freely accessible sequence repositories (four MCV1 and a single MCV2). In comparison to MCV1, a higher degree of nucleotide sequence conservation was observed among MCV2 genomes. Large-scale recombination events were identified in two newly assembled MCV1 genomes and one MCV2 genome. One recombination event was located in a newly identified recombinant region of the viral genome, and all previously described recombinant regions were re-identified in at least one novel MCV genome. MCV genes comprising the identified recombinant segments have been previously associated with viral interference with host T-cell and NK-cell immune responses. In conclusion, the two most common MCV genotypes emerged along divergent evolutionary pathways from a common ancestor, and the differences in the heterogeneity of MCV1 and MCV2 populations may be attributed to the strictness of the constraints imposed by the host immune response.
Assessment of human papillomavirus (HPV) type-specific viral load (VL) is a valid tool for determining the etiology of HPV-related skin tumors, especially when more than one HPV type is detected ...within one lesion.
The causative HPV type was determined in 185 fresh-frozen tissue specimens of histologically confirmed common warts (CWs) collected from 121 immunocompetent patients. All tissues were tested using the type-specific quantitative real-time polymerase chain reactions (PCR) for the most common wart-associated
-PV (HPV2/27/57) and
-PV types (HPV1/63/204). The presence of 23 additional low-risk HPVs was evaluated using a conventional wide-spectrum PCR.
HPV DNA was detected in 176/185 (95.1%) CWs and multiple HPV types in 71/185 (38.4%) lesions. Using the VL approach and a robust cutoff of one viral copy/cell established in this study, HPV2/27/57 were determined as causative agents in 41/53 (77.3%) and 53/71 (74.7%) CWs with single and multiple HPVs, respectively.
CWs are mostly etiologically associated with HPV2/27/57 and only rarely with HPV1. In the majority of CWs containing multiple HPVs, a single HPV type was present in high concentration, indicating etiological association. No significant differences in VLs of lesion-causing HPV types in CWs containing single or multiple HPVs were found.
Hereditary angioedema (HAE) is a rare autosomal dominant disease characterized by swelling of the face, lips, tongue, larynx, genitalia, or extremities, with abdominal pain caused by intra-abdominal ...edema. HAE is caused by mutations affecting the C1 inhibitor gene, SERPING1, resulting in low levels of C1 inhibitor (Type I HAE) or normal levels of ineffective C1 inhibitor (Type II HAE). A nationwide survey identified nine unrelated families with HAE in Slovenia, among whom 17 individuals from eight families were recruited for genetic analyses. A diagnosis of HAE was established in the presence of clinical and laboratory criteria (low C1 inhibitor antigenic levels and/or function), followed up by a positive family history. Genetic studies were carried out using PCR and sequencing to detect SERPING1 mutations in promoter, noncoding exon 1, the 7 coding exons, and exon-intron boundaries. Multiplex ligation-dependent probe amplification was performed in order to search for large deletions/duplications in SERPING1 gene. A mutation responsible for HAE was identified in patients from seven families with the disease. In HAE type I families, one previously reported substitution (Gln67Stop, c.265C>T) and four novel mutations were identified. The new mutations included two missense substitutions, Ser128Phe (c.449C>T), and Glu429Lys (c.1351G>A), together with two frameshift mutations, indel (c.49delGinsTT) and deletion (c.593_594delCT). Both families with HAE type II harbored the two well-known substitutions affecting the arginyl residue at the reactive center in exon 8, Arg444Cys (c.1396C>T) and Arg444His (c.1397G>A), respectively. In one patient only the homozygous variant g.566T>C (c.-21T>C) was identified. Our study identified four novel mutations in the Slovenian HAE population, highlighting the heterogeneity of mutations in the SERPING1 gene causing C1 inhibitor deficiency and HAE. In a single patient with HAE a homozygous variant g.566T>C (c.-21T>C) might be responsible for the disease.