8 research outputs found

    The HIV Envelope but Not VSV Glycoprotein Is Capable of Mediating HIV Latent Infection of Resting CD4 T Cells

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    HIV fusion and entry into CD4 T cells are mediated by two receptors, CD4 and CXCR4. This receptor requirement can be abrogated by pseudotyping the virion with the vesicular stomatitis virus glycoprotein (VSV-G) that mediates viral entry through endocytosis. The VSV-G-pseudotyped HIV is highly infectious for transformed cells, although the virus circumvents the viral receptors and the actin cortex. In HIV infection, gp120 binding to the receptors also transduces signals. Recently, we demonstrated a unique requirement for CXCR4 signaling in HIV latent infection of blood resting CD4 T cells. Thus, we performed parallel studies in which the VSV-G-pseudotyped HIV was used to infect both transformed and resting T cells in the absence of coreceptor signaling. Our results indicate that in transformed T cells, the VSV-G-pseudotyping results in lower viral DNA synthesis but a higher rate of nuclear migration. However, in resting CD4 T cells, only the HIV envelope-mediated entry, but not the VSV-G-mediated endocytosis, can lead to viral DNA synthesis and nuclear migration. The viral particles entering through the endocytotic pathway were destroyed within 1–2 days. These results indicate that the VSV-G-mediated endocytotic pathway, although active in transformed cells, is defective and is not a pathway that can establish HIV latent infection of primary resting T cells. Our results highlight the importance of the genuine HIV envelope and its signaling capacity in the latent infection of blood resting T cells. These results also call for caution on the endocytotic entry model of HIV-1, and on data interpretation where the VSV-G-pseudotyped HIV was used for identifying HIV restriction factors in resting T cells

    New Paths towards Old Dreams: Microphrenology

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    Assessing written work by determining competence to achieve the module-specific learning outcomes.

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    This chapter describes lasers and other sources of coherent light that operate in a wide wavelength range. First, the general principles for the generation of coherent continuous-wave and pulsed radiation are treated including the interaction of radiation with matter, the properties of optical resonators and their modes as well as such processes as Q-switching and mode-locking. The general introduction is followed by sections on numerous types of lasers, the emphasis being on todayʼs most important sources of coherent light, in particular on solid-state lasers and several types of gas lasers. An important part of the chapter is devoted to the generation of coherent radiation by nonlinear processes with optical parametric oscillators, difference- and sum-frequency generation, and high-order harmonics. Radiation in the extended ultraviolet (EUV) and x-ray ranges can be generated by free electron lasers (FEL) and advanced x-ray sources. Ultrahigh light intensities up to 1021 W/cm2 open the door to studies of relativistic laser–matter interaction and laser particle acceleration. The chapter closes with a section on laser stabilization
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