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Open Access Research

Human herpesvirus 6A induces apoptosis of primary human fetal astrocytes via both caspase-dependent and -independent pathways

Bin Gu12, Guo-Feng Zhang12, Ling-Yun Li2, Feng Zhou2, Dong-Ju Feng2, Chuan-Lin Ding3, Jing Chi2, Chun Zhang12, Dan-Dan Guo2, Jing-Feng Wang2, Hong Zhou2, Kun Yao2* and Wei-Xing Hu1*

Author Affiliations

1 Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China

2 Department of Microbiology and Immunology, Nanjing Medical University, Nanjing 210029, China

3 Tumor Immunobiology Program, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA

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Virology Journal 2011, 8:530  doi:10.1186/1743-422X-8-530

Published: 12 December 2011



Human herpesvirus 6 (HHV-6) is a T-lymphtropic and neurotropic virus that can infect various types of cells. Sequential studies reported that apoptosis of glia and neurons induced by HHV-6 might act a potential trigger for some central nervous system (CNS) diseases. HHV-6 is involved in the pathogenesis of encephalitis, multiple sclerosis (MS) and fatigue syndrome. However, the mechanisms responsible for the apoptosis of infected CNS cells induced by HHV-6 are poorly understood. In this study, we investigated the cell death processes of primary human fetal astrocytes (PHFAs) during productive HHV-6A infection and the underlying mechanisms.


HHV-6A can cause productive infection in primary human fetal astrocytes. Annexin V-PI staining and electron microscopic analysis indicated that HHV-6A was an inducer of apoptosis. The cell death was associated with activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP), which is known to be an important substrate for activated caspase-3. Caspase-8 and -9 were also significantly activated in HHV-6A-infected cells. Moreover, HHV-6A infection led to Bax up-regulation and Bcl-2 down-regulation. HHV-6A infection increased the release of Smac/Diablo, AIF and cytochrome c from mitochondria to cytosol, which induced apoptosis via the caspase-dependent and -independent pathways. In addition, we also found that anti-apoptotic factors such as IAPs and NF-κB decreased in HHV-6A infected PHFAs.


This is the first demonstration of caspase-dependent and -independent apoptosis in HHV-6A-infected glial cells. These findings would be helpful in understanding the mechanisms of CNS diseases caused by HHV-6.

Apoptosis; Human herpesvirus 6A; Primary human fetal astrocyte; Caspase