摘要:

Objectives:Human immunodeficiency virus type 1 (HIV-1) Rev is a nucleocytoplasmic shuttling protein with dominant localization in the cell nucleus/nucleolus. To clarify the mechanism(s) that enables such a biased subcellular localization under the co-presence of nuclear/nucleolar targeting (NOS) and nuclear export signals (NES), the properties of another functional domain, a nuclear diffusion inhibitory signal (NIS), was investigated.Study Design:The NIS was previously shown to interfere with passive nuclear entry of small proteins. Intracellular distribution and degradation profiles of Rev mutants that harbor mutations in the NIS were analyzed biochemically and cell-biologically.Results:A NIS-deficient Rev mutant, which was no longer functional as Rev, displayed a significantly more rapid degradation profile as a consequence of its dramatic leakage into the cytoplasm. Additionally, disabling the NOS/nuclear localization signal (NLS), as well as the NIS, resulted in further rapid degradation, which also supports the hypothetical role of the nucleolus as a Rev storage site.Conclusions:It was uncovered that the NIS is playing a key role in HIV-1 Rev function by maintaining the nuclear-dominant localization and the intracellular stability of Rev.Journal of Human Virology 2000;3:173-181 © Lippincott Williams & Wilkins, Inc.

ISSN:1090-9508    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Objective:To assess immunogenicity of recombinant human immunodeficiency virus type 1 (HIV-1) envelope vaccine (rgp 160) in late HIV infection.Study Design/Methods:HIV-infected volunteers (n = 142), with CD4+T lymphocyte counts of <400/mm3, were enrolled in a dose-comparison, open-label trial with stratification by CD4+cell count, randomization to a primary series at two dose levels, and a sub-group receiving interferon-&ggr; (IFN-&ggr;) as an adjuvant. Subjects received booster doses of vaccine over a follow-up period of 18-28 months.Results:At 6 and 12 months, 36% and 38% of participants, respectively, had new or augmented antibody titers (≥4-fold increase) against one or more gp160 epitopes (C1, V3, C41, 448C). Delayed-type hypersensitivity (DTH) to intradermal gp160, initially not present in any participant, developed after immunization in 41%, with higher prevalence in participants receiving the lower dose of vaccine. Both antibody and skin test responses occurred in 20-25% of vaccine recipients. Virtually all antibody and skin test responses occurred in participants with initial CD4+cell counts of >100 cells/mm3. IFN-&ggr; had no significant effect on immune response. Immunization was well tolerated. Trends in CD4+cell count, clinical events, and laboratory findings correlated with baseline CD4+T lymphocyte count stratum and not with immunization regimen. Opportunistic conditions occurred at expected rates. Viral load trends (p24 antigen in all participants and viral RNA by reverse transcription-polymerase chain reaction in a subset of 26 participants) did not correlate with immunization regimen.Conclusion:Immunization of patients with advanced HIV infection with rgp160 resulted in new and augmented humoral and DTH responses, without unexpected significant adverse events or evident clinical benefits attributable to immunization.Journal of Human Virology 2000;3:182-192 © Lippincott Williams & Wilkins, Inc.

ISSN:1090-9508    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Summary:The implementation of human immunodeficiency virus (HIV) vaccine efficacy trials in developing countries represents an unprecedented series of challenges for the medical and scientific communities, health authorities, policy makers, and the populations of diverse countries. Such trials require great attention, dedication, and information at the earliest possible time from many groups in these communities, as well as the clear and full collaboration of all the national and international institutions and agencies involved. This article discusses suggestions and makes recommendations regarding multiple hurdles to trial implementation, including access to appropriate populations, incidence and natural history of HIV type 1 (HIV-1) infection, definition of efficacy endpoints, and logistical, ethical, regulatory, political, and media issues. The conduct of phase I and II trials in developing countries will be a critical step for appropriate vaccine selection and in helping to identify the country- and community-specific issues and the needs for further implementation. Some countries have already established their own national HIV vaccine development plans. Additional operational and action plans with special emphasis on efficacy trial implementation would be strongly recommended after country-specific preparedness workshops and constitution of national or regional task forces.Journal of Human Virology 2000;3:193-214 © Lippincott Williams & Wilkins, Inc.

ISSN:1090-9508    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Objectives:To study the effect of cell differentiation on the vulnerability of human neural cell types to human cytomegalovirus (HCMV) infection.Study Design/Methods:Primary cultures of human fetal neuroepithelial stem cells and differentiating neuroepithelial precursor cells were infected with HCMV strain AD169. Infectious virus production, apoptosis, and viral-associated cytopathic effects then were examined over a 5-day period.Results:HCMV established productive infection in these cells, generating 10-fold amplification of infectious virus. There was no significant difference in the percentage of apoptotic cells in HCMV-infected versus mock-infected cultures. HCMV antigen and specific cytopathic effects were observed in differentiating astrocytes and neurons, although HCMV antigen was 2-fold more frequent among postmitotic neurons.Conclusions:Neuroepithelial precursor cells and differentiating astrocytes and neurons are permissive to cytopathic HCMV infection, suggesting that the fetal human central nervous system is vulnerable to HCMV-induced neuronal injury at its earliest stages of development.Journal of Human Virology 2000;3:215-228 © Lippincott Williams & Wilkins, Inc.

ISSN:1090-9508    

出版商:OVID    

年代:2000

数据来源: OVID