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    Natural polymorphisms of HIV-1 subtype-C integrase coding region in a large group of ARV-naïve infected individuals

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    PURPOSE: Integrase (IN) is an enzyme produced by human immunodeficiency virus (HIV)-1 that enables its genetic material to be integrated into the DNA of the infected cell. Still now, few data are available with detailed analysis of the natural IN polymorphisms of HIV-1 subtype-C in datasets retrieved from antiretroviral-naïve patients; this study focuses on these polymorphisms. METHODS: The analysis included 335 HIV-1 subtype-C IN sequences (one per patient). Multi-alignment of IN sequences was performed, and for the definition of a polymorphism, only amino acid changes with prevalence ≥3 % among treatment-naïve patients were considered. RESULTS: Seventy IN amino acid positions were fully conserved. Differently, forty-six IN amino acid polymorphic positions were observed, 12 within the N-terminal domain and 13 within the C-terminal domain. In the DDE-catalytic motif, only one mutation per site (D64G/D116G/E152K) was found, while a low variability (<1 %) was observed for IN positions interacting with LEDGF/p75. A major drug resistance mutation for raltegravir (RAL) and elvitegravir (EVG), Q148H, was retrieved from one patient and another RAL primary resistance mutation, Y143H, was also retrieved from another patient. CONCLUSIONS: The results from the IN sequences analyzed underlined that some unexpected baseline substitutions affecting the susceptibility to RAL/EVG could be detected in drug-naïve individuals, and, therefore, it should be genotyped before the consideration of HIV-1 IN inhibitors (INIs). The impact of these mutations on the baseline drug susceptibility of HIV-1 subtype-C to INIs may need to be addressed prior to the introduction of these drugs in some Asiatic and African countries

    The novel KI, WU, MC polyomaviruses: possible human pathogens?

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    Recently, three novel human polyomaviruses KIPyV, WUPyV and MCPyV were uncovered in biological specimens of patients with different underlying clinical conditions. Although it is too early to draw firm conclusions on their role in human pathology, this finding has revitalized the scientific debate on the Polyomaviridae family and their relation to human disease. Seroepidemiological studies showed that, similarly to BKPyV and JCPyV, benign primary exposure to these new viruses occurs early in childhood. The viruses then remain latent in the body, and reactivate in immunosuppressed patients with possible pathological consequences. Furthermore, the discovery of MCPyV in a rare and aggressive skin cancer named Merckel cell carcinoma and its clonal integration within the tumor genome suggests that MCPyV infection may represent an early event in the pathogenesis of this disease. This review describes the general aspects of human polyomavirus infection and pathogenesis. Current topics of investigation and future directions in the field are also discussed

    Influenza virus A (H5N1): A pandemic risk?

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    Influenza A subtype H5N1 has represented a growing alarm since its recent identification in Asia. Previously thought to infect only wild birds and poultry, H5N1 has now infected humans, cats, pigs and other mammals in an ongoing outbreak, often with a fatal outcome. In order to evaluate the risk factors for human infection with influenza virus H5N1, here we summarize 53 case patients confirmed with H5N1 infection during 2006. The review also compares the mortality rate among human cases from late 2003 until 15 June 2006 in different countries, Neither how these viruses are transmitted to humans nor the most effective way to reduce the risk for infection is fully understood, The association between household contact with diseased poultry in human infection has been demonstrated, This association could possibly operate by 2 mechanisms. First, transmission may be by inhalation or conjunctival deposition of large infectious droplets which may travel only in short distances, Second, having infected poultry in the home and preparation of infected poultry for consumption may result in exposure to higher virus concentrations than other types of exposure. There is so far no significant evidence for repeated human to human transmission, yet some cases of human to human transmission among the family relatives in Indonesia, Azerbaijan, Iraq and Turkey have been described. Recent outbreaks of highly pathogenic avian influenza A virus (H5N1 sub-type) infections in poultry and humans (through direct contact with infected birds) have raised concerns that a new influenza pandemic might occur in the near future

    Specific VpU codon changes were significantly associated with gp120 V3 tropic signatures in HIV-1 B-subtype

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    After infection and integration steps, HIV-1 transcriptions increase sharply and singly-spliced mRNAs are produced. These encode Env (gp120 and gp41) and auxiliary proteins Vif, Vpr and VpU. The same localization within the unique structure of the mRNAs suggests that the VpU sequence prior to the Env could affect the Env polyprotein expression.The HIV-1 infection process begins when the gp120 subunit of the envelope glycoprotein complex interacts with its receptor(s) on the target cell. The V3 domain of gp120 is the major determinant of cellular co-receptor binding. According to phenotypic information of HIV-1 isolates, sequences from the VpU to V3 regions (119 in R5- and 120 X4-tropic viruses; one per patient) were analysed. The binomial correlation phi coefficient was used to assess covariation among VpU and gp120(V3) signatures. Subsequently, average linkage hierarchical agglomerative clustering was performed. Beyond the classical V3 signatures (R5-viruses: S11, E25D; X4-viruses: S11KR, E25KRQ), other specific V3 and novel VpU signatures were found to be statistically associated with co-receptor usage. Several statistically significant associations between V3 and VpU mutations were also observed. The dendrogram showed two distinct large clusters: one associated with R5-tropic sequences (bootstrap=0.94), involving: (a) H13NP(V3), E25D(V3), S11(V3), T22A(V3) and Q61H(VpU), (b) E25A(V3) and L12F(VpU), (c) D44E(VpU), R18Q(V3) and D80N(VpU); and another associated with X4-tropic sequences (bootstrap=0.97), involving: (i) E25I(V3) and V10A(VpU), (ii) 0-1insV(VpU), H13R(V3), I46L(VpU), I30M(V3) and 60-62del(VpU), (iii) S11KR(V3) and E25KRQ(V3). Some of these pairs of mutations were encoded always by one specific codon. These data indicate the possible VpU mutational patterns contributing to regulation of HIV-1 tropism

    Author response to laboratory detection of MRSA. Comment on "Antibiotic susceptibility of vancomyin and nitrofurantoin in Staphylococcus aureus isolated from burnt patients in Sulaimaniyah, Iraqi Kurdistan"

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    Comment on Antibiotic susceptibility of vancomyin and nitrofurantoin in Staphylococcus aureus isolated from burnt patients in Sulaimaniyah, Iraqi Kurdistan. [New Microbiol. 201

    The novel swine-origin H1N1 influenza A virus riddle: is it a domestic bird H1N1-derived virus?

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    To understand the role of domestic birds in the 2009 H1N1 influenza A outbreak, a phylogenetic analysis of hemagglutinin, neuraminidase and matrix protein genes from human, avian and swine H1N1 viruses was carried out. Analysis of the H1 sequences revealed that the virus evolved most likely from American swine as well as intermixing between Asian swine and American domestic bird H1N1 viruses. Neuroaminidase and matrix protein analysis showed that the H1N1 2009 viruses were more closely related to the H1N1 isolates from Euro-Asiatic domestic birds and swine than wild birds. Domestic birds could act as intermediate hosts of H1N1 reassortants
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