Ablashi D V, Marsh S, Kaplan M, Whitman J E, Pearson G R
Advanced Biotechnologies Inc. Columbia, Md., USA.
Intervirology. 1998;41(1):1-9. doi: 10.1159/000024909.
In order to investigate the levels of HHV-6 infection and elevated antibodies to HHV-6 in HIV-1-infected asymptomatic and symptomatic patients, peripheral blood mononuclear cells were (PBMC) cultured. As patients progressed from asymptomatic HIV infection to AIDS, there was a concurrent increase in replicating HHV-6. Plasma obtained from several of these patients showed the presence of IgM antibody and a significantly elevated level of HHV-6 IgG antibody. Serial samples of plasma from 10 AIDS patients collected over a period of 4 years were assayed for the detection of HHV-6 core protein (gp116/64/54) by antigen capture ELISA. The results demonstrated that either a persistent infection or reactivation can occur based on the degree of fluctuation in HHV-6 antigen detected. ELISA to HHV-6 purified viral proteins, i.e., early (p41/38) and late (gp110), demonstrated that IgG antibody to gp110 did not differentiate between HIV-1-infected and healthy donors. IgG and IgM antibody to p41/38, however, showed a significantly higher prevalence in HIV-1-infected individuals (56.7-85.3%) than in normal healthy donors (19.0%), suggesting virus activation. PBMC culture from the AIDS patients expressing significant peaks of HHV-6 core antigen (gp116/64/54) in their plasma showed that in most cases, HHV-6 early and late antigens were detectable; however, those patients with consistently low antigen peaks had no detectable antigens in their PBMC. Only 55% of PBMC cultures established from IgM antibody-positive HIV-1-infected asymptomatic and AIDS patients expressed HHV-6 antigens in the short-term cultures, but HHV-6 antigens could not be demonstrated in PBMC culture from 4 IgM-antibody-positive healthy donors. HHV-6 isolates obtained from the HIV-1-positive patients were predominantly HHV-6 variant A, compared to healthy donors. Based on the data presented here, it is evident that the levels of HHV-6 infection increased in HIV-1-infected asymptomatic individuals as they progressed to AIDS. Our immunovirological data on HHV-6-infected individuals with HIV infection support a role for HHV-6 in the pathogenesis of AIDS. We believe that simultaneous active infection with HIV-1 and HHV-6 may contribute to enhanced immune suppression perhaps leading to disease manifestations.
为了研究人类疱疹病毒6型（HHV-6）在人类免疫缺陷病毒1型（HIV-1）感染的无症状和有症状患者中的感染水平以及HHV-6抗体升高情况，对外周血单个核细胞（PBMC）进行了培养。随着患者从无症状HIV感染进展为艾滋病，HHV-6复制同时增加。从其中一些患者获得的血浆显示存在IgM抗体以及HHV-6 IgG抗体水平显著升高。对10名艾滋病患者在4年期间采集的系列血浆样本进行检测，通过抗原捕获酶联免疫吸附测定（ELISA）检测HHV-6核心蛋白（gp116/64/54）。结果表明，根据检测到的HHV-6抗原波动程度，可能发生持续感染或再激活。针对HHV-6纯化病毒蛋白（即早期蛋白p41/38和晚期蛋白gp110）的ELISA显示，针对gp110的IgG抗体在HIV-1感染患者和健康供体之间没有差异。然而，针对p41/38的IgG和IgM抗体在HIV-1感染个体中的流行率（56.7 - 85.3%）显著高于正常健康供体（19.0%），提示病毒激活。来自血浆中HHV-6核心抗原（gp116/64/54）表达显著峰值的艾滋病患者的PBMC培养显示，在大多数情况下，可检测到HHV-6早期和晚期抗原；然而，那些抗原峰值持续较低的患者在其PBMC中未检测到抗原。从IgM抗体阳性的HIV-1感染无症状和艾滋病患者建立的PBMC培养物中，只有55%在短期培养中表达HHV-6抗原，但在4名IgM抗体阳性健康供体的PBMC培养物中未证明有HHV-6抗原。与健康供体相比，从HIV-1阳性患者分离出的HHV-6主要是HHV-6 A变体。根据此处呈现的数据，很明显，在HIV-1感染的无症状个体进展为艾滋病时，HHV-6感染水平增加。我们关于HHV-6感染的HIV感染个体的免疫病毒学数据支持HHV-6在艾滋病发病机制中的作用。我们认为，HIV-1和HHV-6同时活跃感染可能导致免疫抑制增强，也许会引发疾病表现。
