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In vitro activity of candidate microbicides against cell-associated HIV
No full textMost research on HIV transmission and microbicides focuses on the inhibition of cell-free virus (CFV) present in genital secretions. However, an effective microbicide should also block the transmission of cell-associated virus (CAV) originating from seminal T-cells and macrophages. Because inhibition of CAV remains controversial, especially for viral entry inhibitors, we developed a novel in vitro assay to evaluate the activity of different classes of candidate microbicides against cell-free HIV and HIV-infected leucocytes (i.e, resting PBMC, activated PBMC and monocyte-derived macrophages). The assay is based on two CD4+ CXCR4+ T-cell lines (R5MaRBLE and X4MaRBLE) that both contain a firefly luciferase reporter gene but differ in the expression of the CCR5 co-receptor. Consequently, the quantification of luciferase activity and Gag p24 concentration in co-cultures of R5-tropic HIV-infected leucocytes with each cell line separately allowed to discriminate between the infection of the cell-lines (i.e., target cells), the ongoing infection in the HIV-infected leucocytes (i.e., effector cells), and the total infection of the co-culture (i.e., effector + target cells). All fourteen antiretrovirals tested, were able to block target cell infection by all three sources of CAV, although a small decrease in activity (2 to 18-fold) was observed for all entry inhibitors. On the other hand, the production of Gag p24 by the infected effector cells could only be blocked by protease inhibitors. Overall, these results show that entry and protease inhibitors are eligible drug classes for inclusion in future combination microbicides
Theileria parva isolate of low virulence infects a subpopulation of lymphocytes
No full textTheileria parva is a tick-transmitted protozoan parasite that infects and transforms bovine lymphocytes. We have previously shown that Theileria parvaChitongo (TpC) is an isolate of lower virulence than T.parvaMuguga (TpM). Lower virulence appeared correlated with a delayed onset of thelogarithmic growth phase of TpC-tranformedperipheral blood mononuclear cells after in vitro infection. In the current study, infection experiments of WC1(+)-gammadelta-T cellsrevealed thatonly TpMcould infect these cells andthat no transformed cells could be obtained withTpC sporozoites. Subsequent analysis of susceptibility of different cell lines and purified populations of lymphocytes for infection and transformation by both isolates showed that TpMsporozoites could attach and infectCD4(+), CD8(+) and WC1(+) T lymphocytes, but that TpCsporozoites were only observed to bind to the CD8(+) T cell population. Flow cytometry analysis of established,transformed clones confirmed this bias in target cells. TpM-transformed clones consisted of different cell surface phenotypes, suggesting that they were derived from either host CD4(+), CD8(+)or WC1(+)T cells. In contrast, all in vitro and in vivoTpC-transformed clones expressed CD8 but not CD4 or WC1, suggesting that the TpC-transformed target cells were exclusivelyinfected CD8(+) lymphocytes.So a role of cell tropism in virulence is likely. Since the adhesion molecule p67 is 100 % identical between the two strains, a second, high affinity adhesin that determines target cell specificity appears to exist
Leishmania (Viannia) species identification on clinical samples from cutaneous leishmaniasis in Peru: assessment of a molecular step-wise approach
No full textWe present an algorithm based on three PCR assays for Leishmania (Viannia) species identification and assessed its performance using 70 specimens from Peruvian patients. The succession of the assayed targets can be ordered according to species prevalence. Sequential progression through the algorithm reduced the number of samples here studied by approximately 30% after each step
Management of chronic diseases in sub-Saharan Africa: cross-fertilisation between HIV/AIDS and diabetes care
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