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RISS 인기검색어
- 검색키워드
- 저자 : Birx, Deborah L. (검색결과 2 건)
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Liu, Fengliang,Fan, Xiuzhen,Auclair, Sarah,Ferguson, Monique,Sun, Jiaren,Soong, Lynn,Hou, Wei,Redfield, Robert R.,Birx, Deborah L.,Ratto-Kim, Silvia,Robb, Merlin L.,Kim, Jerome H.,Michael, Nelson L.,H Public Library of Science 2016 PLoS pathogens Vol.12 No.6
<▼1><P>Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen <I>Candida albicans (C</I>. <I>albicans)</I> is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, <I>C</I>. <I>albicans-specific</I> CD4 T cells are highly permissive to HIV <I>in vitro</I>. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on <I>C</I>. <I>albicans</I>- and CMV-specific CD4 T-cell immunity <I>in vivo</I>. We found a sequential dysfunction and preferential depletion for <I>C</I>. <I>albicans-</I>specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of <I>C</I>. <I>albicans-</I>specific CD4 T cells were more permissive to HIV <I>in vitro</I> and impaired earlier in HIV-infected subjects. Infection history analysis showed that <I>C</I>. <I>albicans-</I>specific CD4 T cells were more susceptible to HIV <I>in vivo</I>, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that <I>C</I>. <I>albicans-</I>specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis.</P></▼1><▼2><P><B>Author Summary</B></P><P>HIV infection is closely associated with enhanced host susceptibility to various opportunistic infections (OIs), among which mucosal candidiasis caused by the fungal pathogen <I>Candida albicans</I> (<I>C</I>. <I>albicans</I>) is an early and common manifestation. Even in the era of effective ART, mucosal candidiasis is still a clinically relevant presentation in HIV-infected patients. The underlying mechanisms are not well defined. CD4-mediated immunity is the major host defense mechanism against <I>C</I>. <I>albicans</I>. We here investigated a group of ART naïve, HIV-infected human subjects and examined longitudinally the impact of HIV on <I>C</I>. <I>albicans</I>-specific CD4 T-cell immunity as compared to CD4 T-cell immunity specific for CMV, another opportunistic pathogen that usually does not cause active disease in early HIV infection. We found that <I>C</I>. <I>albicans</I>-specific CD4 T cells were more susceptible to HIV <I>in vivo</I> and were preferentially depleted in progressive HIV-infected individuals as compared to CMV-specific CD4 T cells. Of importance, we also found that in these HIV-infected subjects <I>C</I>. <I>albicans</I>-specific CD4 T cell response manifested a sequential dysfunction with earlier impairment of Th17, but not Th1, functions. Our study suggests an immunological basis that helps explain the earlier and more common onsets of mucosal candidiasis in progressive HIV-infected patients.</P></▼2>
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HIV-1 Genetic Diversity Among Incident Infections in Mbeya, Tanzania
Billings, Erik,Sanders-Buell, Eric,Bose, Meera,Kijak, Gustavo H.,Bradfield, Andrea,Crossler, Jacqueline,Arroyo, Miguel A.,Maboko, Leonard,Hoffmann, Oliver,Geis, Steffen,Birx, Deborah L.,Kim, Jerome H. MARY ANN LIEBERT INC PUBL 2017 AIDS RESEARCH AND HUMAN RETROVIRUSES Vol.33 No.4
<P><B>Abstract</B></P><P>In preparation for vaccine trials, HIV-1 genetic diversity was surveyed between 2002 and 2006 through the Cohort Development study in the form of a retrospective and prospective observational study in and around the town of Mbeya in Tanzania's Southwest Highlands. This study describes the molecular epidemiology of HIV-1 strains obtained from 97 out of 106 incident HIV-1 infections identified in three subpopulations of participants (one rural, two urban) from the Mbeya area. Near full-genome or half-genome sequencing showed a subtype distribution of 40% C, 17% A1, 1% D, and 42% inter-subtype recombinants. Compared to viral subtyping results previously obtained from the retrospective phase of this study, the overall proportion of incident viral strains did not change greatly during the study course, suggesting maturity of the epidemic. A comparison to a current Phase I-II vaccine being tested in Africa shows ∼17% amino acid sequence difference between the gp120 of the vaccine and subtype C incident strains. Phylogenetic and recombinant breakpoint analysis of the incident strains revealed the emergence of CRF41_CD and many unique recombinants, as well as the presence of six local transmission networks most of which were confined to the rural subpopulation. In the context of vaccine cohort selection, these results suggest distinct infection transmission dynamics within these three geographically close subpopulations. The diversity and genetic sequences of the HIV-1 strains obtained during this study will greatly contribute to the planning, immunogen selection, and analysis of vaccine-induced immune responses observed during HIV-1 vaccine trials in Tanzania and neighboring countries.</P>
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