Interactions between human immunodeficiency virus type 1 and vaccinia virus in human lymphoid tissue ex vivo.
Interactions between human immunodeficiency virus type 1 and vaccinia virus in human lymphoid tissue ex vivo.
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离体人体淋巴组织中 1 型人类免疫缺陷病毒与牛痘病毒之间的相互作用。
DOI：
10.1128/jvi.00326-07
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发表时间：
2007
影响因子：
5.4
通讯作者：
Brichacek,Beda
中科院分区：
文献类型：
--
作者：
Vanpouille,Christophe;Biancotto,Angelique;Lisco,Andrea;Brichacek,Beda
牛痘病毒（VACV）不仅作为各种疫苗的载体，而且由于其潜在的生物恐怖制剂用途而成为一种针对天花的免疫工具，近年来引起了人们的关注。很明显，尽管对疫苗病毒的研究已有很长的历史，但其组织发病机制仍有待充分了解。在此，我们研究了VACV的发病机制及其在人类淋巴组织中与人类免疫缺陷病毒1型（HIV-1）的相互作用。我们发现离体培养的扁桃体组织支持纽约市卫生委员会菌株（Dryvax疫苗的VACV菌株）的生产性感染。在感染后的12天内，VACV容易感染T淋巴细胞和非T (B)淋巴细胞，并相等地耗尽这两种亚群的细胞。在T淋巴细胞中，CD8+细胞根据其优先感染而优先耗尽：CD8+T细胞被有效感染的概率几乎是CD4+T细胞的6倍。表达CCR5和活化标记CD25、CD38和HLA-DR的T细胞是VACV在淋巴组织中感染的其他主要靶点。因此，VACV主要抑制共感染组织中r5sf162表型HIV-1的复制，因为R5-tropic HIV-1需要激活CCR5+CD4+细胞才能产生感染。体外感染VACV的人淋巴组织可用于研究VACV与其他病毒，特别是HIV-1的相互作用，并评估各种VACV载体，以开发重组疫苗。
Vaccinia virus (VACV) has been attracting attention recently not only as a vector for various vaccines but also as an immunization tool against smallpox because of its potential use as a bioterrorism agent. It has become evident that in spite of a long history of studies of VACV, its tissue pathogenesis remains to be fully understood. Here, we investigated the pathogenesis of VACV and its interactions with human immunodeficiency virus type 1 (HIV-1) in the context of human lymphoid tissues. We found that ex vivo-cultured tonsillar tissue supports productive infection by the New York City Board of Health strain, the VACV strain of the Dryvax vaccine. VACV readily infected both T and non-T (B) lymphocytes and depleted cells of both of these subsets equally over a 12-day period postinfection. Among T lymphocytes, CD8+cells are preferentially depleted in accordance with their preferential infection: the probability that a CD8+T cell will be productively infected is almost six times higher than for a CD4+T cell. T cells expressing CCR5 and the activation markers CD25, CD38, and HLA-DR are other major targets for infection by VACV in lymphoid tissue. As a consequence, VACV predominantly inhibits the replication of the R5SF162phenotype of HIV-1 in coinfected tissues, as R5-tropic HIV-1 requires activated CCR5+CD4+cells for productive infection. Human lymphoid tissue infected ex vivo by VACV can be used to investigate interactions of VACV with other viruses, in particular HIV-1, and to evaluate various VACV vectors for the purpose of recombinant vaccine development.