HTLV-2 Induces Resistance to CCR5-Dependent HIV-1 Infection Via Selective PBMC Expression of CCL3L1

Background In HIV-1/HTLV-2 co-infected IDUs the CCL3/MIP-1alpha induction by HTLV-2 leads to HIV inhibition. CCL3 gene codes for CCL3/LD78alpha and CCL3L1/LD78beta isoforms. CCL3L1 binds more potently to CCR5 than any other chemokine. Possession of a CCL3L1 copy number lower than two (the population average for Europeans) is associated with markedly enhanced HIV/AIDS susceptibility. Here, we analysed the genotype frequency of CCL3L1 and its expression in 8 HTLV-2-infected/HIV-1exposed-seronegative (HTLV-2/HIV-1ESN) individuals, 7 LTNP-HIV-1/HTLV-2-co-infected and 8 LTNP-HIV-1mono-infected subjects

Molecular and phylogenetic analysis of HIV-1 variants circulating in Italy

<p>Abstract</p> <p>Objective</p> <p>The continuous identification of HIV-1 non-B subtypes and recombinant forms in Italy indicates the need of constant molecular epidemiology survey of genetic forms circulating and transmitted in the resident population.</p> <p>Methods</p> <p>The distribution of HIV-1 subtypes has been evaluated in 25 seropositive individuals residing in Italy, most of whom were infected through a sexual route during the 1995–2005 period. Each sample has been characterized by detailed molecular and phylogenetic analyses.</p> <p>Results</p> <p>18 of the 25 samples were positive at HIV-1 PCR amplification. Three samples showed a nucleotide divergence compatible with a non-B subtype classification. The phylogenetic analysis, performed on both HIV-1 <it>env </it>and <it>gag </it>regions, confirms the molecular sub-typing prediction, given that 1 sample falls into the C subtype and 2 into the G subtype. The B subtype isolates show high levels of <it>intra</it>-subtype nucleotide divergence, compatible with a long-lasting epidemic and a progressive HIV-1 molecular diversification.</p> <p>Conclusion</p> <p>The Italian HIV-1 epidemic is still mostly attributable to the B subtype, regardless the transmission route, which shows an increasing nucleotide heterogeneity. Heterosexual transmission and the interracial blending, however, are slowly introducing novel HIV-1 subtypes. Therefore, a molecular monitoring is needed to follow the constant evolution of the HIV-1 epidemic.</p

Antibody Complementarity-Determining Regions (CDRs) Can Display Differential Antimicrobial, Antiviral and Antitumor Activities

Background: Complementarity-determining regions (CDRs) are immunoglobulin (Ig) hypervariable domains that determine specific antibody (Ab) binding. We have shown that synthetic CDR-related peptides and many decapeptides spanning the variable region of a recombinant yeast killer toxin-like antiidiotypic Ab are candidacidal in vitro. An alanine-substituted decapeptide from the variable region of this Ab displayed increased cytotoxicity in vitro and/or therapeutic effects in vivo against various bacteria, fungi, protozoa and viruses. the possibility that isolated CDRs, represented by short synthetic peptides, may display antimicrobial, antiviral and antitumor activities irrespective of Ab specificity for a given antigen is addressed here.Methodology/Principal Findings: CDR-based synthetic peptides of murine and human monoclonal Abs directed to: a) a protein epitope of Candida albicans cell wall stress mannoprotein; b) a synthetic peptide containing well-characterized B-cell and T-cell epitopes; c) a carbohydrate blood group A substance, showed differential inhibitory activities in vitro, ex vivo and/or in vivo against C. albicans, HIV-1 and B16F10-Nex2 melanoma cells, conceivably involving different mechanisms of action. Antitumor activities involved peptide-induced caspase-dependent apoptosis. Engineered peptides, obtained by alanine substitution of Ig CDR sequences, and used as surrogates of natural point mutations, showed further differential increased/unaltered/decreased antimicrobial, antiviral and/or antitumor activities. the inhibitory effects observed were largely independent of the specificity of the native Ab and involved chiefly germline encoded CDR1 and CDR2 of light and heavy chains.Conclusions/Significance: the high frequency of bioactive peptides based on CDRs suggests that Ig molecules are sources of an unlimited number of sequences potentially active against infectious agents and tumor cells. the easy production and low cost of small sized synthetic peptides representing Ig CDRs and the possibility of peptide engineering and chemical optimization associated to new delivery mechanisms are expected to give rise to a new generation of therapeutic agents.Department of Education, Universities and Research, Basque GovermentFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Istituto Superiore di Sanita, National Research Project on A.I.D.S.Cariparma Banking FoundationBrazilian National Research CouncilUniv Parma, Sez Microbiol, Dipartimento Patol, I-43100 Parma, ItalyUniv Basque Country, Fac Med Odontol, Dept Inmunol, Microbiol Parasitol, Bilbao, SpainUniv Basque Country, Dept Enfermeria I, Bilbao, SpainUniv Milan, Dipartimento Sci Cliniche L Sacco, Sez Malattie Infettive Immunopatol, Milan, ItalyUniv Studi Parma, Dipartimento Clin Med, Nefrol Sci Prev, Parma, ItalyUniversidade Federal de São Paulo, Departamento Microbiol, Imunol Parasitol, Unidade Oncol Expt, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, São Paulo, BrazilUniversidade Federal de São Paulo, Departamento Microbiol, Imunol Parasitol, Unidade Oncol Expt, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, São Paulo, BrazilDepartment of Education, Universities and Research, Basque Goverment: IT-264-07FAPESP: 06/50634-2Istituto Superiore di Sanita, National Research Project on A.I.D.S.: 50G.30Istituto Superiore di Sanita, National Research Project on A.I.D.S.: 40D.14Cariparma Banking Foundation: 2004.0190Brazilian National Research Council: research fellowshipWeb of Scienc

Neoplastic lymphangiosis of the upper aerodigestive tract simulating field cancerization: histopathological analysis, surgical limits and literature review

Neoplastic lymphangiosis is defined as extensive embolic spread of cancer cells in the lymphatic vessels often without any evidence of a mass. Instead, field cancerization is defined by the presence of multifocal neoplastic lesions in a mucosal field previously exposed to mutagenic factors. In this case report, this oncological entity was suggested by the wide extent and multifocality of the disease and by the patient's exposure to risk factors. Instead, the pathological slides revealed the integrity of the mucosa and the presence of widespread embolic metastasis to lymphatic vessels. Thus, the diagnosis was changed to neoplastic lymphangiosis. This clinical presentation is a negative prognostic factor, and surgical treatment is ineffective because of the impossibility to obtain adequate free margins. The present case underlines the poor prognosis of such locally advanced cancer and the importance of recognizing it early so that the treatment approach can be adapted