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Biomedical subjects

F Mammano

Publications and source records attributed to F Mammano.

59 records · Page 4Linked to original sources

Synthetic peptides from the principal neutralizing domain of human immunodeficiency virus type 1 (HIV-1) enhance HIV-1 infection through a CD4-dependent mechanism.

The principal neutralizing domain (PND) of Human Immunodeficiency Virus type 1 (HIV-1) is mapped to a 24-amino acid sequence located in the hypervariable V3 region of the viral envelope protein. The PND of HIV-1 isolates from infected individuals corresponds mostly to that of the HIV-1 MN strain. We found that a peptide designed from the PND of HIV-1 MN virus greatly enhanced viral infection, while a peptide-derived PND of HTLV-IIIB virus showed at least 10-fold less efficient activity; no such effect was exhibited by the other peptides tested, including one designed from the PND of HIV-1 RF strain. The observed enhancing effect occurred in the early steps of viral infection and was not strain-restricted as both MN- and IIIB-derived peptides increased heterologous virus expression, including that of the RF strain. The MN- and, to a lesser extent, IIIB-derived peptides also increased CD4 expression on the cell membrane and differentially inhibited CD4 down-regulation induced by the phorbol ester TPA and/or by the monosialoganglioside GM1; the peptides showing no viral infection enhancement had no such effects. These findings demonstrate that the viral enhancement observed took place through a CD4-dependent mechanism and suggest that the PND is involved in HIV-1 infection and spread.

Amino Acid Sequence↗

Serological and molecular evidence of infection by human T-cell lymphotropic virus type II in Italian drug addicts by use of synthetic peptides and polymerase chain reaction.

Infection with human T lymphotropic virus type I (HTLV-I) is associated with specific forms of tumours and neurological disorders, but the pathogenic activity of HTLV-II is not yet established. Moreover, due to high crossreactivity between the two viruses, differential diagnosis is not readily achieved. To discriminate between HTLV-I and HTLV-II infections, we employed synthetic peptides specific for HTLV-I and HTLV-II env regions, and the polymerase chain reaction (PCR). In a series of 962 intravenous drug addicts (IVDAs) and 50 patients with haematological malignancies, 51 and 2 samples, respectively, were reactive against HTLV-I proteins; among these, HTLV-I infection was confirmed only in 1 patient with adult T-cell lymphoma, while HTLV-II infections were identified in 6 out of 14 PCR-tested IVDAs. These findings provide evidence of HTLV-II infection among Italian IVDAs. The differentiation between HTLV-I and HTLV-II infections may contribute to a better understanding of HTLV-II pathogenicity in man.

AIDS Serodiagnosis↗

Antigen detection, virus culture, polymerase chain reaction, and in vitro antibody production in the diagnosis of vertically transmitted HIV-1 infection.

Polymerase chain reaction (PCR), virus culture (V), antigen detection (Ag), and in vitro antibody production (IVAP) assays may be useful for the early detection of vertically transmitted HIV-1 infection in infants under 18 months of age, when a diagnosis cannot be based on seropositivity because of maternal antibody persistence. To assess the reliability of these procedures and to correlate diagnostic results with infection status, 101 children born to HIV-1-seropositive mothers were evaluated by all these techniques within the first 6 months of life. The children were then followed up to the age of at least 18 months, when diagnosis was made on the basis of AIDS or AIDS-related complex (ARC) onset or persistence of HIV-1 seropositivity. Out of 27 children classified as infected according to the above criteria, 25 (92.5%) were repeatedly positive in IVAP test, 22 (81.5%) in the first PCR analysis, and only 19 (70.3%) in the initial V assay. On further testing, a total of 24 children (88.9%) were found positive in PCR assay, and 23 (85.2%) in V test. All these assays were found to be more sensitive than antigen detection for HIV-1 infection diagnosis, but the antigenaemia was shown to be a useful prognostic marker of disease onset. We also found that both Ag and IVAP assays could give false-positive results in the first 2 months of life, which severely limits their diagnostic value during this period of time. False-positive results in PCR assay could occur at any time of the tested period and were unrelated to the child's age.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

Infection of Epstein-Barr virus-transformed lymphoblastoid B cells by the human immunodeficiency virus: evidence for a persistent and productive infection leading to B cell phenotypic changes.

Four Epstein-Barr virus-positive lymphoblastoid cell lines (LCL) were successfully infected in vitro with immunodeficiency virus type 1 (HIV-1) as demonstrated by reverse transcriptase activity and p24 HIV antigen in culture supernatants, positive cell staining for gag-encoded HIV proteins, presence of viral HIV genome by Southern blot analysis and ulstrastructural observations. In addition, both HIV-1-infected B cells and their supernatants efficiently transactivated the chloramphenicol acetyl transferase reporter gene which is under the control of the HIV-1 long terminal repeat. The LCL cells displayed long-term HIV-1 infection and production, but no cytopathic effects were observed. Cytofluorimetric analysis did not detect membrane CD4 presence in the LCL cells before and after HIV-1 infection; moreover, a minute amount of CD4 mRNA was observed only in one of the LCL. A monoclonal antibody specific for the viral binding site of the CD4 molecule delayed, but did not block, HIV-1 infection of the LCL cells. Following HIV-1 infection, changes in LCL phenotype were observed, consisting of a decrease in CD23- and CD39-positive cells, and a concomitant increase of cells with surface CD10 and Bac-1. Furthermore, HIV-1-infected LCL cells did not grow in tight clumps, as usually observed in uninfected LCL, but as disperse suspensions, and formed more agar colonies than control LCL. However, despite this apparent acquisition of a malignant-like phenotype, c-myc proto-oncogene rearrangement was not detected. The appearance of cells with new characteristics did not seem due to clone selection by HIV-1 infection, since all the LCL conserved their clonotypic pattern of IgH chain rearrangement. The acquisition of malignant-like features by HIV-infected B cells might be clinically significant in terms of the pathogenesis of non-Hodgkin's B cell lymphomas, which occur frequently in AIDS patients.

Antigens, Differentiation, B-Lymphocyte↗