Merkel Cell Polyomavirus DNA Detection in Respiratory Samples: Study of a Cohort of Patients Affected by Cystic Fibrosis

Abstract

Background: The role of Merkel cell polyomavirus (MCPyV) as a respiratory pathogen is controversial, and it is still unclear in patients with cystic fibrosis (CF). The aim of this study was to define the MCPyV prevalence and epidemiology in CF patients in order to gain new insights into the association between MCPyV infection and respiratory diseases. Methods: A one-year study was conducted testing oropharyngeal aspirate samples from 249 and 124 CF and non-CF patients, respectively. Detection of MCPyV was carried out by nested polymerase chain reaction (PCR). Moreover, a sequence alignment to examine viral capsid protein 1 (VP1) and a phylogenetic analysis were performed. Results: MCPyV DNA was detected in 65 out of 249 samples analyzed CF (26%), a percentage that was higher than that recorded in non-CF patients (0.8%). There were no statistically significant differences in MCPyV prevalence according to gender, while there was a correlation between MCPyV detection and age. Interestingly, an association between the presence of MCPyV and the concurrent isolation of Staphylococcus aureus was found. Sequence analysis of MCPyV VP1 and phylogenetic analysis revealed a 99% homology with the published sequences of these viruses in GenBank. Conclusions: Detection of MCPyV in CF patient specimens pointed out a possible interaction between the virus and CF. Further studies are necessary to fully understand the involvement of MCPyV in the pathogenesis of respiratory disorders.

Genetic Diversity of the Noncoding Control Region of the Novel Human Polyomaviruses

“…In contrast to NCCR analysis conducted on rectal swabs from an HIV-1-positive population, which were characterized by the onset of transitions, transversions, and single or double deletions [110], MCPyV NCCR in stool samples from patients with hematological disorders exhibited a high degree of sequence stability, thereby suggesting that sequence rearrangements occurred rarely in the gastrointestinal anatomical site [113]. To date, although it is well documented that MCPyV DNA has been detected in the upper and lower respiratory tract specimens of children and adults and in immunocompetent and immunocompromised patients [114][115][116][117][118] and that the detection of MCPyV DNA was also observed in cystic fibrosis patient respiratory secretions [119,120], the respiratory NCCR structure organization has not yet been investigated.…”

Merkel Cell Polyomavirus (MCPyV) in the Context of Immunosuppression: Genetic Analysis of Noncoding Control Region (NCCR) Variability among a HIV-1-Positive Population

“…Merkel cell polyomavirus (MCPyV) is a small, nonenveloped, double-stranded DNA virus, identified in 2008 [2] and related to the progenitors BK polyomavirus (BKPyV) and JC polyomavirus (JCPyV). Most MCPyV infections are asymptomatic, and serological studies showed that 50-80% of the healthy individuals present MCPyV-specific antibody responses [3,4]. After primary infection, HPyVs establish a lifelong persistence in different anatomical sites, such as lymphoid tissue (JCPyV), renal epithelium (JCPyV and BKPyV), and skin (MCPyV) [5].…”

“…After primary infection, HPyVs establish a lifelong persistence in different anatomical sites, such as lymphoid tissue (JCPyV), renal epithelium (JCPyV and BKPyV), and skin (MCPyV) [5]. Recently, a high prevalence of MCPyV has also been found in respiratory and stool samples from immunocompromised patients, adding important information on MCPyV prevalence and persistence in the respiratory and gastrointestinal tract [4][5][6][7][8]. MCPyV shares the genomic structure of BKPyV and JCPyV, with a circular genome divided into three functional regions: early, late, and interposed between these regions, the noncoding control region (NCCR).…”

“…MCPyV does not seem to express virus protein 3 (VP3), and virions do not seem to contain VP3, despite an in-frame internal adenin-timin-guanine (ATG) start codon in the VP2 gene [9]. The NCCR contains the origin of replication and bidirectional promoter elements [4,10,11]. The two main spliced products, LT and sT antigens, are involved in the viral infectious cycle, in cell cycle progression, and in malignant transformation of the host cell [12].…”

Decreased IgG Antibody Response to Viral Protein Mimotopes of Oncogenic Merkel Cell Polyomavirus in Sera From Healthy Elderly Subjects

“…Despite these conflicting rates, previous studies concordantly imply that MCPyV appears to be almost ubiquitous in the general population, which is asymptomatically infected ( 18 , 27 , 30 , 31 ). After primary infection, which occurs during childhood ( 28 , 32 , 33 ), MCPyV establishes a lifelong but inoffensive infection in healthy individuals ( 32 , 34 ). However, in certain circumstances, such as immune system impairment in the host, increased viral activity can occur.…”