Valentina Daprà

Changes in the Messenger RNA Expression of Toll-Like Receptors 2 and 4 in Healthy Infants According to Age

Background Toll‐like receptors (TLRs) are potentially useful indicators of several pediatric disease states. Here, we explore the mechanisms by which inflammation is regulated by interactions between microbiota and the host. Little data are available regarding the expression of TLRs in postnatal healthy infants. TLR 2 and TLR4 are extracellular TLRs that act as innate immune receptors by recognizing a wide range of endogenous ligands and microorganisms. Methods The aim of this study was to use real‐time polymerase chain reaction to investigate the expression of the messenger RNAs (mRNAs) of TLR2 and TLR4 in blood samples obtained from healthy full‐term infants and toddlers. Results We analyzed the mRNA expression levels of TLRs in 88 healthy term children separated according to age. The median expression level of TLR2 was 1.49 ± 1.10 arbitrary units (AU) (n = 25) in infants younger than 3 months, 0.67 ± 0.72 AU (n = 25) in infants aged between 3 and 12 months, and 0.03 ± 0.02 AU (n = 38) in infants older than 12 months. The median expression level of TLR4 was 1.25 ± 0.79 AU (n = 25) in infants younger than 3 months, 0.75 ± 0.54 AU (n = 25) in infants aged 3 to 12 months, and 0.44 ± 0.28 AU (n = 38) in infants older than 12 months. There was difference in the mRNA expression level of TLR2 and TLR4 between infants aged 0 to 3 and 3 to 12 months and those aged more than 1 year (p < 0.0001 and p < 0.0001, respectively) Conclusion We found that the expression levels of TLR2 and TLR4 were associated with age. In particular, we observed that their expression increased during the suckling period and then clearly decreased once the infants reached 1 year of age (p < 0.001). These findings could be related to microbial colonization and the immune system.

Aichivirus in Children with Diarrhea in Northern Italy

Objective: Since its discovery, Aichivirus (AiV) A has been detected, with an incidence of 0.9–4.1%, primarily when studying outbreaks of diarrhea in children or young adults. In this paper, we report the first detection of AiV in Piedmont, Italy, in pediatric patients. Methods: A total of 159 fecal specimens (from 96 males and 63 females) previously screened for rotaviruses, adenoviruses, noroviruses, human parechoviruses, saliviruses, and sapoviruses were collected from infants and children with acute gastroenteritis. Results: The most commonly detected virus was norovirus GII (33.80%), fol lowed by rotavirus (21.30%), astrovirus (18.87%), boca virus (13.92%), sapovirus (10.90%), parechovirus (8%), norovirus GI (6.70%), adenovirus (1%), and salivirus (0.52%). Real-time polymerase chain reaction detected AiV A in 1 (0.62%) case subjects. AiV A was detected in monoinfection only in January. Conclusions: Our results indicate that AiV may be associated with a limited number of diarrhea cases in pediatric patients.

Is HERV-K and HERV-W expression regulated by mir-155 in Sézary syndrome?

BACKGROUND According to the latest update, 2578 unique mature miRNAs are currently annotated in the human genome and participate in the regulation of multiple events, such as cellular proliferation or apoptosis. A previous study analyzing global miRNA expression patterns in GH cells (high HERV-K versus low) showed that two miRNAs (miR-663 and miR-638) are differentially regulated and exhibit expression parallel to that of HERV-K. The aim of this study was to evaluate HERV-K and -W pol gene and mir-155 expression in SS patients and possible relationship between them. METHODS The comparison between SS patients and healthy donor showed a significant difference in terms of mir-155 expression p=0.0003 as previously reported by our groups. RESULTS We demonstrated that HERV-K and -W pol gene expression was significantly higher in SS patients vs healthy donor as previously reported by our groups. Our correlation data suggest that miR-155 are not directly involved in regulating the HERVs. CONCLUSIONS Furthermore, further studies including other cohorts of pathology with mir-155 and HERVs involvement such as inflammatory diseases are needed to investigate the role of mir-155 in the cross-activations of HERVs.

MW polyomavirus in diarrheal Italian infants

BACKGROUND MXPyV, like MWPyV, was identified in stool samples from children suffering diarrhea in Mexico. In this study, we used a home-made real time PCR to investigate the presence of this novel viruses in stool specimen collected from under-Five- Year-Old Children with gastroenteritis. METHODS A total of 192 fecal specimens previously screened for RV, ADV, NoV, HPeV and SaV, were tested for MWPyV with Taqman real time PCR. RESULTS The most commonly detected virus was NoV GII (33.8%), followed by RV (21.3%), SaV (10.9%), HPeV(8%), NoV GI (6.7%) and AdV (1%). Real time PCR detected MWPyV in 1/192 (0.5%) patients. CONCLUSIONS We detected MWPyV in 0.5% of fecal specimens collected from pediatric patients suffering gastroenteritis which is smaller than the previously reported in literature (4.4% in Australia and 12% Mexico).

Prevalence and Clinical Profile of Human Salivirus in Children with Acute Gastroenteritis in Northern Italy, 2014–2015

Objective: Human Salivirus (SalV) has been associated with gastroenteritis on all continents. Methods: This paper presents the real-time RT-PCR assay for the detection of SalV in clinical fecal samples collected from 192 hospitalized children with acute gastroenteritis in Piedmont, Italy. Results: The most commonly detected virus was Norovirus genogroup II (GII) (33.8%), followed by Rotavirus (21.3%), Sapovirus (10.9%), Parechovirus (8%), Norovirus GI (6.7%), and Adenovirus (1%). PCR detected SalV in 1 (0.5%) subject. Conclusions: Our data show that the detection rate of SalV in diarrheal children (0.5%) is lower than that observed in other countries, where it is reported in diarrheal children in 8.6–1.2% of patients.

Is HERV-K and HERV-W Expression Regulated by miR-155 in Kidney Transplant Patients with Human Cytomegalovirus Infection?

According to the latest update, 2,578 unique mature microRNAs (miRNAs) are currently annotated in the human genome and participate in the regulation of multiple events, such as cellular proliferation or apoptosis. A previous study analyzing global miRNA expression patterns in GH cells (high human endogenous retrovirus, HERV, K vs. low) showed that 2 miRNAs (miR-663 and miR-638) are differentially regulated and exhibit expression parallel to that of HERV-K. The aim of this study was to evaluate HERV-K and -W pol gene and miR-155 expression in kidney transplant recipients and the possible relationship between them. The comparison between kidney transplant patients negative for human cytomegalovirus (HCMV) infection and positive patients showed a significant difference in terms of miR-155 expression (p = 0.0111). We demonstrated that HERV-K and -W pol gene expression was significantly higher in CMV-infected kidney transplant recipients versus those not infected as previously reported by our groups. Our correlation data suggest that miR-155 are not directly involved in regulating the HERV notwithstanding that we together observed increased expression of HERV-K and -W and diminished expression of miR-155 in HCMV-infected human kidney transplant recipients.

DNA from Human Polyomaviruses, MWPyV, HPyV6, HPyV7, HPyV9 and HPyV12 in Cutaneous T-cell Lymphomas

Background/Aim: The etiopathogenesis of mycosis fungoides and Sézary syndrome remains obscure. Different viruses have been proposed to have a role in the etiopathogenesis of cutaneous T-cell lymphomas (CTCL). In the present study, the presence of five recently discovered human polyomaviruses 6 (HPyV6), human polyomaviruses 7 (HPyV7), human polyomaviruses 9 (HPyV9), human polyomaviruses 12 (HPyV12), and Malawi polyomavirus (MWPyV), have been analyzed in 55 CTCL in order to confirm the skin tropism and the possible pathological association of these new polyomaviruses. Materials and Methods: Human polyomaviruses DNA were amplified from skin lesions were recovered from a total of 55 patients (32 males and 23 females, average age 63±15 years) affected by CTCL. Results: When assayed for the presence of 5 different HPyVs, (HPyV6, HPyV7, HPyV9, MWPyV, and HPyV12) HPyV9, HPyV10 and HPyV12 DNA sequences were not found in any skin specimens. HPyV6 and 7 DNA was detected in 1/55 (1.8%) of skin specimens. Conclusion: The low-level presence of HPyV6 and HPyV7 DNA, and lack of detection of polyomaviruses HPyV9, MWPyV and HPyV12 in our series do not support a significant role of these HPyVs subtypes in the etiopathogenesis of skin cancers.

miR‐155 expression in Primary Cutaneous T‐Cell Lymphomas (CTCL)

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Expression of the pol gene of human endogenous retroviruses HERV-K and -W in leukemia patients

The human endogenous retroviruses (HERVs) are a family of endogenous retroviruses that integrated into the germ cell DNA of primates over 30 million years ago. HERV expression seems impaired in several diseases, ranging from autoimmune to neoplastic disorders. The purpose of this study was to evaluate the overall endogenous retroviral transcription profile in bone marrow (BM) samples. A total of 30 paediatric high-risk leukaemia patients (lymphoid and myeloid malignancies) were tested for HERVs virus gene expression. Our findings show that HERV-K expression was significantly higher in leukaemia patients when compared to healthy donors of a similar median age. We observed a significantly high expression of HERV-K in acute lymphoblastic leukemia (ALL) patients. In this study, we also found a relative overexpression of the endogenous retrovirus HERV-K in BM cells from the majority of leukemia samples analyzed, in particular in ALL. This overexpression might be related to lymphatic leukemogenesis and it warrants further investigations.