This study began when principal investigator Steven Zeichner of Children's National Medical Center and George Washington University in Washington, DC, followed up earlier findings that high concentrations of the antibiotic doxycycline can induce apoptosis, and can also activate replication by the Kaposi's Sarcoma-associated Herpes-virus (KSHV), and a study by his former mentor, Bernard Roizman of the University of Chicago, which showed that apoptosis also triggers replication of herpes simplex virus-1, which causes cold sores in the mouth.
"We decided to test... several additional human herpes-viruses that cause notable diseases and which have good latent infection cell line models, including human herpes-viruses (HHV)-6A, =6B, and -7, and Epstein-Bar virus (EBV)," says Zeichner. That all of these herpes-viruses were activated by apoptosis suggested that this mechanism might apply to all herpes-viruses.
The clinical implications could be staggering. Some important cytotoxic cancer chemotherapeutic drugs, including doxorubicin, vincristine, and prednisone act in part by inducing apoptosis, according to the study. Additionally, treatment with glucocorticoids has been known to worsen Kaposi's Sarcoma. The investigators also note that herpesvirus activation has been associated with poor outcomes following bone marrow transplantation.
"Activation of herpes-viruses in these states and disorders has previously been variably attributed to general immune suppression, suppression of specific arms of the immune system, and increased concentrations of inflammatory and activating cytokines," write the researchers in the article. "If this activation occurs in potentially damaging ways, then perhaps patients at risk for herpes-virus activation should be treated with antiviral medications in addition to antineoplastic cytotoxic chemotherapy."
Almost all humans are infected with HHV-6, and many are infected with the other aforementioned herpes-viruses, as well as cytomegalovirus, oral and genital herpes, and Varicella zoster, the virus that causes chicken pox and shingles.
Source: Eurekalert
