RESUMO
Molnupiravir, an oral direct-acting antiviral effective in vitro against SARS-CoV-2, has been largely employed during the COVID-19 pandemic, since December 2021. After marketing and widespread usage, a progressive increase in SARS-CoV-2 lineages characterized by a higher transition/transversion ratio, a characteristic signature of molnupiravir action, appeared in the Global Initiative on Sharing All Influenza Data (GISAID) and International Nucleotide Sequence Database Collaboration (INSDC) databases. Here, we assessed the drug effects by SARS-CoV-2 whole-genome sequencing on 38 molnupiravir-treated persistently positive COVID-19 outpatients tested before and after treatment. Seventeen tixagevimab/cilgavimab-treated outpatients served as controls. Mutational analyses confirmed that SARS-CoV-2 exhibits an increased transition/transversion ratio seven days after initiation of molnupiravir. Moreover we observed an increased G->A ratio compared to controls, which was not related to apolipoprotein B mRNAediting enzyme, catalytic polypeptide-like (APOBEC) activity. In addition, we demonstrated for the first time an increased diversity and complexity of the viral quasispecies.
Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , Citidina/análogos & derivados , Genoma Viral , Hidroxilaminas , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , SARS-CoV-2/efeitos dos fármacos , Antivirais/uso terapêutico , Antivirais/farmacologia , Hidroxilaminas/farmacologia , Hidroxilaminas/uso terapêutico , Masculino , Feminino , Estudos de Casos e Controles , Pessoa de Meia-Idade , Citidina/uso terapêutico , Citidina/farmacologia , Idoso , Adulto , Sequenciamento Completo do Genoma , Variação Genética , Uridina/farmacologia , COVID-19/virologia , MutaçãoRESUMO
BACKGROUND: The objective is to show variations in the number of non-tenured personnel (NTP) in a public health research centre (IRCCS) between 30th June 2016 and 31st December 2017. In this time interval, the issue of NTP was at the centre of governmental discussions. METHODS: Data collection was performed from CVs and scientific publications of NTP working at the Fondazione IRCCS Istituto Nazionale dei Tumori (INT). We compared the characteristics of NTP entering or leaving INT and those of NTP who remained in the considered time interval. RESULTS: NTP in INT counted 465 members of staff at 30th June 2016 and 472 at 31st December 2017. 75% of these works in the research. 26% of NTP left INT and their position resulted entirely substituted by other NTP. NTP staff who left are mainly aged under 40 and show fewer publications than those who stayed. Newly acquired NTP are younger and show a fewer number of publications compared to the personnel who left. CONCLUSIONS: 1 out of 4 NTP members of staff moved to a new job during a period in which the uncertain future of NTP research staff was under the spotlight. It appears that IRCCS are progressively being identified as suitable for hands-on, post university internships from which researchers would then choose to move, in search of a new job in public or private centres, with a consequent decline of IRCCS' role in health research.
Assuntos
Reorganização de Recursos Humanos/estatística & dados numéricos , Saúde Pública , Pesquisadores/estatística & dados numéricos , Pesquisa/estatística & dados numéricos , Adulto , Fatores Etários , Feminino , Humanos , Itália , Masculino , Pesquisa/organização & administração , Pesquisadores/organização & administraçãoRESUMO
West Nile virus (WNV) is currently circulating in several European countries and, over recent decades, concomitantly with enhanced surveillance studies and improved diagnostic capabilities, an increase in the geographical distribution and in the number of cases in Europe has been documented. In Italy in 2011, 14 human cases of WNV neuroinvasive infections due to lineage 1 strains were registered in several Italian regions. Here we report WNV partial sequences obtained from serum samples of two patients living in different regions of Italy (Veneto and Sardinia). Phylogenetic analysis, performed on a fragment (566 nt) of the envelope gene, showed that WNV strains circulating in Italy in 2011 belong to lineage 1a, but are different from lineage 1a strains isolated in 2008-2009.The data reported here are consistent with the hypothesis of multiple recent introductions of WNV lineage 1a strains into Italy.
Assuntos
Variação Genética , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/classificação , Vírus do Nilo Ocidental/genética , Análise por Conglomerados , Genótipo , Humanos , Itália , Dados de Sequência Molecular , Filogenia , RNA Viral/genética , Análise de Sequência de DNA , Proteínas do Envelope Viral/genética , Vírus do Nilo Ocidental/isolamento & purificaçãoRESUMO
To determine the lineage of West Nile virus that caused outbreaks in Italy in 2008 and 2009, several West Nile virus strains were isolated from human specimens and sequenced. On the basis of phylogenetic analyses, the strains isolated constitute a distinct group within the western Mediterranean cluster.
Assuntos
Filogenia , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/classificação , Vírus do Nilo Ocidental/genética , Humanos , Itália , Proteínas do Envelope Viral/genética , Proteínas não Estruturais Virais/genética , Vírus do Nilo Ocidental/isolamento & purificaçãoRESUMO
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus responsible for the first autochthonous Italian outbreak in 2007. A226V mutation in E1 has been associated with enhanced replication in A. albopictus vector. Possible involvement of this mutation in enhanced infection capability in primate cells and sensitivity to exogenous interferon (IFN)-a was investigated. No significant differences were observed between the two isolates in terms of replication kinetic, virus yield and cytopathic effect (CPE). Interestingly, the A226V-carrying strain was more susceptible to the antiviral action of recombinant IFN-a. The interplay between A226V mutation and innate defence mechanisms needs further investigation.
Assuntos
Infecções por Alphavirus/virologia , Vírus Chikungunya/genética , Interferon Tipo I/farmacologia , Mutação de Sentido Incorreto , Proteínas do Envelope Viral/genética , Infecções por Alphavirus/imunologia , Animais , Vírus Chikungunya/efeitos dos fármacos , Vírus Chikungunya/patogenicidade , Vírus Chikungunya/fisiologia , Chlorocebus aethiops , Humanos , Interferon Tipo I/genética , Proteínas Recombinantes , Células Vero , Proteínas do Envelope Viral/imunologia , Replicação Viral/genéticaRESUMO
Among 544 HIV-positive women screened for HPV-DNA between 2003 and 2005, 265 (48.7%) were HPV-positive: 24 (9.1%) harboured HPV-16, 21 (7.9%) HPV-31, 12 (4.5%) HPV-18, 7 (2.6%) HPV-33. E6 and E7 of these HPV types were sequenced to assess their diversity. Ranges of inter- and intra-variant diversity were 1.2-3-3%, and 0.8-1.8 for E6 and 0.6-2.7%, and 0.6-2.0% for E7, respectively. HPV-31, the second most common HPV type, showed the highest diversity for both regions. On the whole, 26 out of 59 mutations were non-synonymous. The variability of these proteins may have implications in HPV vaccine strategies.
Assuntos
Genes Virais , Infecções por HIV/complicações , HIV-1 , Proteínas Oncogênicas Virais/genética , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Adulto , Colo do Útero/virologia , Feminino , Variação Genética , Humanos , Itália , Papillomaviridae/classificação , Proteínas E7 de Papillomavirus/genéticaRESUMO
RT-PCR is the most sensitive assay for diagnosis of influenza, due to enhanced rapidity and sensitivity as compared to classical methods. Hemi-nested RT-PCR was developed, targeting NP gene for influenza A and NS gene for influenza B, based on a previous single round RT-PCR method. The new method was compared with the previous technique for analytical sensitivity and specificity, and was applied to clinical samples from the lower and upper respiratory tract. The analytical sensitivity of hemi-nested RT-PCR was 10 (influenza A) and 4 times (influenza B) higher than the previous method. A high specificity of the new hemi-nested RT-PCR assay was observed by using whole respiratory viruses. When applied to lower respiratory tract specimens, the new method showed an increased rate of positivity as compared to the previous technique (9.3% versus 0.7% for influenza A, and 0.9% versus 0.2% for influenza B). Screening of upper respiratory tract samples collected during the seasonal 2005-2006 outbreak indicated 26.4% and 5.8% positivity for influenza A and B, respectively. The results were confirmed by sequence analysis: apart from influenza B, both influenza A subtypes H3N2 and H1N1, associated with the seasonal outbreak, were detected.
Assuntos
Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Primers do DNA , Surtos de Doenças , Genes Virais , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza A/genética , Vírus da Influenza B/genética , Influenza Humana/epidemiologia , Itália/epidemiologia , Proteínas do Nucleocapsídeo , Nucleoproteínas/genética , Proteínas de Ligação a RNA/genética , Sistema Respiratório/virologia , Estações do Ano , Sensibilidade e Especificidade , Proteínas do Core Viral/genética , Proteínas não Estruturais Virais/genéticaRESUMO
Human herpesvirus 8 (HHV-8) antibodies were detected in 1 of 33 patients with pulmonary hypertension (including in 1 of 16 with idiopathic pulmonary arterial hypertension), 5 of 29 with cystic fibrosis, and 3 of 13 with interstitial lung disease. No relationship between HHV-8 infection and pulmonary hypertension was found.