Effects of infections on the pathogenesis of cancer.

Several studies have shown an inverse relationship between acute infections and cancer development. On the other hand, there is a growing evidence that chronic infections may contribute significantly to the carcinogenesis. Factors responsible for increased susceptibility to infections may include modifications of normal defence mechanisms or impairment of host immunity due to altered immune function, genetic polymorphisms, ageing and malnourishment. Studies have demonstrated that children exposed to febrile infectious diseases show a subsequent reduced risk for ovarian cancer, melanoma and many other cancers, while common acute infections in adults are associated with reduced risks for melanoma, glioma, meningioma and multiple cancers. Chronic inflammation associated with certain infectious diseases has been suggested as a cause for the development of tumours. Mechanisms of carcinogenesis due to infections include cell proliferation and DNA replication by mitogen-activated protein kinase pathway, production of toxins that affect the cell cycle and lead to abnormal cell growth and inhibition of apoptosis. This review was aimed to summarize the available evidence on acute infections as a means of cancer prevention and on the role of chronic infections in the development and progression of cancer.

Molecular detection of canine bufaviruses in wild canids.

Novel protoparvoviruses genetically related to human and non-human primate bufaviruses (BuVs) have been detected recently in respiratory and enteric specimens collected from dogs and cats. In this study, by molecular screening of archival collections of faecal samples from wolves and foxes, we detected BuVs with a rate of 17.1% (7/41) and 10.5% (9/86), respectively. Sequence analysis of a portion of the ORF2 gene region of nine positive samples showed that the viruses in these samples were closely related to BuVs (97.5-99.0% nucleotide sequence identity) found in domestic carnivores.

Novel Parvovirus Related to Primate Bufaviruses in Dogs.

A novel protoparvovirus species, related genetically to human bufaviruses, was identified in dogs with respiratory signs. The canine bufavirus was distantly related to the well-known canine protoparvovirus, canine parvovirus type 2, sharing low amino acid identities in the nonstructural protein 1 (40.6%) and in the capsid protein 1 (33.4%). By screening collections of fecal, nasal, and oropharyngeal samples obtained from juvenile dogs (<1 year of age), canine bufavirus DNA appeared as a common component of canine virome. The virus was common in the stool samples of dogs with or without enteric disease and in the nasal and oropharyngeal swab samples of dogs with respiratory signs. However, the virus was not detected in nasal and oropharyngeal swab samples from animals without clinical signs.

Serological and molecular investigation of 2117-like vesiviruses in cats.

Vesivirus 2117 was first discovered as a contaminant in Chinese hamster ovary (CHO) cell cultures used for human drug production. Similar vesiviruses (VeVs) have been detected recently in dogs. In order to address the hypothesis that cats may also be exposed to 2117-like VeVs, in this study, we screened 236 feline sera using an enzyme-linked immunosorbent assay (ELISA) based on a recombinant VP1 protein from the canine VeV Bari/212/07/ITA. IgG antibodies against the 2117-like VeV were detected in 37.3% of the sera tested. Also, by screening cat faecal specimens, the RNA of a 2117-like VeV was detected in a clinically healthy cat.

First molecular identification of kobuviruses in wolves (Canis lupus) in Italy.

Canine kobuviruses (CaKoVs) were first identified in diarrhoeic and asymptomatic dogs in 2011 in the USA. Subsequent studies have demonstrated a worldwide distribution of these viruses, but it is not clear if CaKoVs play a role as enteric pathogens of dogs. More recently, CaKoV RNA has been detected in wild carnivores, including red fox, golden jackal, side-striped jackal and spotted hyena. In this study, we addressed the hypothesis that wolves are susceptible to CaKoV infections. A total of 185 wolf stool samples were collected from necropsied animals and from transects in the Liguria, Piemonte and Valle D'Aosta regions of Italy, and CaKoV RNA was identified in two of these specimens. Both samples were obtained from necropsied wolves, with a prevalence rate of 4.9% (2/41). Sequence analysis of the full-length VP1 region showed that these strains displayed the highest nucleotide (nt) sequence identity (86.3-98.5%) to canine strains identified in the UK and Africa, and to kobuviruses that were previously detected in other African wild carnivores. This suggests that genetically related CaKoV strains circulate in domestic and wild carnivores, with interspecies transmission being not uncommon among carnivores of different ecosystems.

First molecular evidence of kobuviruses in goats in Italy.

By screening 139 rectal swabs collected from either asymptomatic or diarrhoeic goats in Italy, we identified kobuvirus RNA in eight samples (5.8 %). Higher positivity rates were observed in diarrhoeic goats (6.5 %, 3/46) than in asymptomatic animals (5.4 %, 5/93), although the difference was not statistically significant. Based on the analysis of a portion of the 3D gene, four strains were found to share the highest nucleotide (nt) sequence identity with bovine kobuviruses (95.0-98.0 %), which had been detected previously in calves in the UK and Korea. Interestingly, two strains were genetically related to the newly discovered caprine kobuviruses (83.0-97.0 % nt sequence identity), which had been identified in black goats in Korea and in roe deer in Italy. Taken together, these findings demonstrate that kobuviruses are common enteric viruses of goats, although their clinical relevance remains to be investigated.

Detection and genetic characterization of hepatitis E virus (HEV) genotype 3 subtype c in wild boars in Italy.

Hepatitis E virus (HEV) was detected in stools collected from wild boars in Italy, with an overall prevalence of 1.5 % (3/196). The sequence of a ~3.0-kb portion at the 3' end of the genome of one such strain, HEV/WB/P6-15/ITA, was determined. In the full-length ORF2, which encodes the capsid protein, the virus was genetically closest to wild boar and human HEV strains currently classified as genotype 3 subtype c. Interestingly, the 3' end of ORF2 of the WB/P6-15/ITA matched the 340-nucleotide (nt) sequence (94.0 % nt identity) of the human strain PeGe, identified in 2015 from a patient with acute hepatitis E in Genoa, Italy, suggesting that similar HEV strains are circulating in the same geographical setting in humans and animals.

Detection and Full-Length Genome Characterization of Novel Canine Vesiviruses.

Vesiviruses have been detected in several animal species and as accidental contaminants of cells. We detected vesiviruses in asymptomatic kennel dogs (64.8%) and symptomatic (1.1%) and asymptomatic (3.5%) household dogs in Italy. The full-length genome of 1 strain, Bari/212/07/ITA, shared 89%-90% nt identity with vesiviruses previously detected in contaminated cells.

Identification of a Bovine Enteric Calicivirus, Kirklareli Virus, Distantly Related to Neboviruses, in Calves with Enteritis in Turkey.

A calicivirus was detected in neonatal calves with enteritis in Kirklareli, Thrace, Turkey. In the full-length genome, Kirklareli virus was related (48% nucleotide identity) to bovine enteric caliciviruses (Nebovirus genus). The virus was also detected in a herd in Ankara, Central Anatolia, but not in other Turkish prefectures.

Molecular detection of kobuviruses in European roe deer (Capreolus capreolus) in Italy.

Kobuvirus RNA was found in 6.6 % (13/198) of stool specimens from roe deer (Capreolus capreolus) captured during the regular hunting season. Upon sequence analysis of a fragment of the 3D gene, nine strains displayed the highest nucleotide sequence identity (91.2-97.4 %) to bovine kobuviruses previously detected in either diarrhoeic or asymptomatic calves. Interestingly, four strains were genetically related to the newly discovered caprine kobuviruses (84.2-87.6 % nucleotide identity) identified in black goats in Korea.

Seroprevalence of norovirus genogroup IV antibodies among humans, Italy, 2010-2011.

Noroviruses (NoVs) of genogroup IV (GIV) (Alphatron-like) cause infections in humans and in carnivorous animals such as dogs and cats. We screened an age-stratified collection of serum samples from 535 humans in Italy, using virus-like particles of genotypes GIV.1, circulating in humans, and GIV.2, identified in animals, in ELISA, in order to investigate the prevalence of GIV NoV-specific IgG antibodies. Antibodies specific for both genotypes were detected, ranging from a prevalence of 6.6% to 44.8% for GIV.1 and from 6.8% to 15.1% for GIV.2 among different age groups. These data are consistent with a higher prevalence of GIV.1 strains in the human population. Analysis of antibodies against GIV.2 suggests zoonotic transmission of animal NoVs, likely attributable to interaction between humans and domestic pets. This finding, and recent documentation of human transmission of NoVs to dogs, indicate the possibility of an evolutionary relationship between human and animal NoVs.

Molecular evidence of kobuviruses in free-ranging red foxes (Vulpes vulpes).

Red foxes (Vulpes vulpes) are susceptible to viral diseases of domestic carnivores. In this study, by screening rectal swabs collected from 34 red foxes in Italy, we identified kobuvirus RNA in five samples. Based on analysis of partial RdRp and full-length VP1 genes, all of the strains shared the highest identity with canine kobuviruses (CaKVs) recently detected in the US, the UK and Italy. These findings provide the first evidence of the circulation of these novel viruses in foxes.

Genetic heterogeneity of bovine noroviruses in Italy.

By screening 104 faecal samples from asymptomatic calves in Italy, bovine norovirus RNA was detected with a prevalence rate of 10.5 % (11/104). A continuous sequence spanning the RdRp region and the 5' end of the capsid gene was generated for 7 of the 11 strains. Upon phylogenetic analysis, five strains were grouped with GIII.2 Newbury2-like viruses, and one strain was grouped with GIII.1 Jena-like noroviruses. Interestingly, one strain (80TE/IT) was genetically related to the GIII.1/Jena/80/De in the RdRp but resembled the GIII.2/Newbury2/76/UK in the capsid gene, suggesting a recombination event occurring in the ORF1/ORF2 junction region.

Circoviridae Survey in Captive Non-Human Primates, Italy.

Circoviruses (CVs) and cycloviruses (CyVs), members of the family Circoviridae, have been identified only occasionally in non-human primates (NHPs). In this study, we investigated the presence and genetic features of these viruses in 48 NHPs housed in the Bioparco-Rome Zoological Garden (Italy) and in the Anima Natura Wild Sanctuary Semproniano (Grosseto, Italy), testing fecal, saliva, and serum samples with a broadly reactive consensus nested PCR able of amplifying a partial region of the replicase (Rep) gene of members of the family Circoviridae. Viral DNA was detected in a total of 10 samples, including a saliva swab and 9 fecal samples collected, respectively from five Japanese macaques (Macaca fuscata) and four mandrills (Mandrillus sphinx), with an overall prevalence of 18.7% (9/48). On genome sequencing, five strains revealed the highest nucleotide identity (98.3-98.6%) to a CyV strain (RI196/ITA) detected in the intestinal content of a Maltese wall lizard (Podarcis filfolensis) in Italy. Although the origin of the Italian NHP strains, genetically distant from previously detected NHP CyVs, is uncertain, our results also highlight that the virome of captive animals is modulated by the different dietary and environmental sources of exposure.

Molecular Surveillance for Bocaparvoviruses and Bufaviruses in the European Hedgehog (Erinaceus europaeus).

The presence of bocaparvoviruses (BoVs) and bufaviruses (BuVs) in the European hedgehog (Erinaceus europaeus) was investigated by screening duodenal and liver samples collected from 183 carcasses, delivered to wildlife rescue centers located in northwestern Italy. BoV DNA was detected in 15 animals (8.2%), with prevalences of 7.1% (13/183) and 2.7% (5/183) in intestine and liver samples, respectively. Upon the sequence analyses of the NS1 gene, two highly divergent BoVs (65.5-67.8% nt identities) were identified. Fourteen strains showed the highest identity (98.3-99.4% nt) to the hedgehog BoV strains recently detected in China in Amur hedgehogs (Erinaceus amurensis), whilst four strains were genetically related (98.9-99.4% nt identities) to the porcine BoVs identified in pigs and classified in the species Bocaparvovirus ungulate 4, which included related viruses also found in rats, minks, shrews, and mice. BuV DNA was detected in the duodenal samples of two hedgehogs, with a prevalence rate of 1.1%. The nearly full-length genome of two BuV strains, Hedgehog/331DU-2022/ITA and Hedgehog/1278DU/2019/ITA, was reconstructed. Upon phylogenetic analysis based on the NS and VP aa sequences, the Italian hedgehog BuVs tightly clustered with the BuVs recently identified in the Chinese Amur hedgehogs, within a potential novel candidate species of the genus Protoparvovirus.

Molecular detection of Aichi virus in raw sewage in Italy.

Aichi virus (AiV) is suspected to play a role in viral gastroenteritis in humans. In this study, we assessed the presence of AiV in untreated influent sewage samples collected at four wastewater treatment plants in central Italy. AiV was detected in 6 (12.5 %) of the 48 specimens and in all plants. All of the Italian strains showed the highest nucleotide and amino acid sequence identity to genotype B AiV detected recently in Asia, especially in China.

A parathyroid cancer with soporous state, depression, and severe cognitive decline in acute renal failure.

Key Clinical Message: Soporous state in acute renal failure represent an atypical presentation of parathyroid cancer. Complete prompt investigations and diagnosis have a fundamental role in the management of this disease. Abstract: This report describes a case of parathyroid carcinoma (PC) with an uncommon first clinical presentation: soporous state, depression, and severe cognitive decline in association with acute renal failure. After discovering extremely high serum calcium and parathyroid hormone (PTH) levels, the diagnosis of primary hyperparathyroidism (pHPT) was made and a surgical en bloc resection was performed. After the surgical intervention, the histological examination revealed the presence of a malignant parathyroid disease, thus confirming our first preoperative suspicion.

Exploring the Enteric Virome of Cats with Acute Gastroenteritis.

Viruses are a major cause of acute gastroenteritis (AGE) in cats, chiefly in younger animals. Enteric specimens collected from 29 cats with acute enteritis and 33 non-diarrhoeic cats were screened in PCRs and reverse transcription (RT) PCR for a large panel of enteric viruses, including also orphan viruses of recent identification. At least one viral species, including feline panleukopenia virus (FPV), feline enteric coronavirus (FCoV), feline chaphamaparvovirus, calicivirus (vesivirus and novovirus), feline kobuvirus, feline sakobuvirus A and Lyon IARC polyomaviruses, was detected in 66.1% of the samples.. Co-infections were mainly accounted for by FPV and FCoV and were detected in 24.2% of the samples. The virome composition was further assessed in eight diarrhoeic samples, through the construction of sequencing libraries using a sequence-independent single-primer amplification (SISPA) protocol. The libraries were sequenced on Oxford Nanopore Technologies sequencing platform. A total of 41 contigs (>100 nt) were detected from seven viral families infecting mammals, included Parvoviridae, Caliciviridae, Picornaviridae, Polyomaviridae, Anelloviridae, Papillomaviridae and Paramyxoviridae, revealing a broad variety in the composition of the feline enteric virome.

Serological and Molecular Survey on Domestic Dog Hepadnavirus in Household Dogs, Italy.

The discovery of hepadnaviruses in cats (domestic cat hepadnavirus, DCH) and of a DCH-like virus in dogs has raised several questions regarding the role of these viruses in pets, with particular emphasis on their potential impact on animal health and epidemiology, as well as possible zoonotic implications. In this study, by screening an age-stratified collection of 600 canine serum samples for DCH with an ELISA assay based on the recombinant core antigen (DCHCAg), specific antibodies were found with an overall prevalence of 10.0% (60/600), with a higher prevalence in younger and older dogs. By retesting the canine DCHCAbs-positive sera with an ELISA test based on the recombinant surface protein of DCH (DCHSAg), a total of 18 sera (30%, 18/60) also contained IgG anti-DCHSAg. All the sera were also assessed molecularly using either a consensus hepadnavirus PCR or a specific real-time PCR for DCH. Hepadnavirus DNA was detected in four seronegative dogs, with a prevalence rate of 0.7% (4/600). On sequence analysis of the polymerase region amplified with pan-hepadnavirus primers, the amplicons displayed the highest nucleotide identity (97.3-99.6%) to DCH sequences detected in cats and to the domestic dog hepadnavirus recently identified in a canine serum sample from Italy.

Detection at high prevalence of newlavirus (protoparvovirus) in the carcasses of red foxes.

Wildlife conservation also relies on the study of animal virome. We identified the DNA of a novel fox protoparvovirus, newlavirus, with high (71%) prevalence in the carcasses of red foxes. On genome sequencing, high genetic diversity and possible recombination was observed, suggesting complex evolutionary dynamics in wildlife.