SECRETORY LEUKOCYTE PROTEASE INHIBITOR - A HUMAN SALIVA PROTEIN EXHIBITING ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS-1 ACTIVITY IN-VITRO

SECRETORY LEUKOCYTE PROTEASE INHIBITOR - A HUMAN SALIVA PROTEIN EXHIBITING ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS-1 ACTIVITY IN-VITRO
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DOI:
10.1172/jci118056
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发表时间:
1995-07-01
影响因子:
15.9
通讯作者:
WAHL, SM
WAHL, SM
中科院分区:
医学1区
文献类型:
--
作者:
MCNEELY, TB;DEALY, M;WAHL, SM

文献摘要

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在人唾液存在下,粘附的原代单核细胞被HIV-1(Ba-L)感染被显著抑制。通过逆转录酶(RT)水平,唾液虽然在单核细胞病毒暴露期间仅存在1小时,但在感染后3周抑制HIV-1感染,而人血浆和滑液不能抑制HIV-1感染。在唾液可溶性级分中鉴定出抗病毒活性,在这些检测的蛋白质中,发现只有分泌性白细胞蛋白酶抑制剂(SLPI)在生理浓度下具有抗HIV-1活性,SLPI抗HIV-1活性是剂量依赖性的,在1-10 μ g/ml时具有最大抑制(RT活性抑制> 90%),SLPI还部分抑制增殖的人T细胞中的HIV-1(IIIB)感染,SLPI似乎靶向宿主细胞相关分子,因为不能证明与病毒蛋白的相互作用。然而,SLPI的抗HIV-1活性不是由于与CD 4抗原的直接相互作用或下调CD 4抗原,SLPI在整个唾液中的部分消耗导致唾液的抗HIV-1活性降低。这些数据表明,SLPI具有抗逆转录病毒活性,并且可能有助于唾液的重要抗病毒活性,该活性与HIV-1的不频繁的经口传播相关。
Infection of adherent primary monocytes with HIV-1(Ba-L) is significantly suppressed in the presence of human saliva, By reverse transcriptase (RT) levels, saliva, although present for only 1 h during monocyte viral exposure, inhibited HIV-1 infectivity for 3 wk after infection, whereas human plasma and synovial fluid failed to inhibit HIV-1 infectivity, Antiviral activity was identified in the saliva soluble fraction, and to determine the factor(s) responsible, individual saliva proteins were examined, Of those proteins examined, only secretory leukocyte protease inhibitor (SLPI) was found to possess anti-HTV-1 activity at physiological concentrations, SLPI anti-HIV-l activity was dose dependent, with maximal inhibition at 1-10 mu g/ml (> 90% inhibition of RT activity), SLPI also partially inhibited HIV-1(IIIB) infection in proliferating human T cells, SLPI appears to target a host cell-associated molecule, since no interaction with viral proteins could be demonstrated. However, SLPI anti-HIV-1 activity was not due to direct interaction with or downregulation of the CD4 antigen, Partial depletion of SLPI in whole saliva resulted in decreased anti-HIV-1 activity of saliva, These data indicate that SLPI has antiretroviral activity and may contribute to the important antiviral activity of saliva associated with the infrequent oral transmission of HIV-1.