Liquorice compound beats latent herpesvirus

Liquorice compound beats latent herpesvirus

Newsdesk that is the decision we stand by today.” But because this was only a single patient, critics have questioned the wisdom of making a public a...

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that is the decision we stand by today.” But because this was only a single patient, critics have questioned the wisdom of making a public announcement before all of the data have been assembled and analysed. Similar case studies have also been reported, including two Canadian patients with drug-resistant and rapidly progressing HIV strains. (AIDS 2003; 17: 1256–58) “The case in New York seems to be an extension of what we previously reported”, said Julio Montaner (University of British Columbia, Vancouver, BC, Canada), who treated both patients. “The patient in New York has more resistance and has progressed within a shorter period of time.”

Montaner points out that a small percentage of patients infected with wild-type virus can have very rapid progression, while a small percentage can have very slow progression. “So it’s not clear right now if the cases that we are starting to see truly represent the beginning of a new epidemic, or a supervirus as such.” Ho stated that it has been known for a number of years that the transmission of multidrug-resistant (MDR) virus is possible, as is rapid progression following acute infection. In this case, there appeared to be a convergence of the MDR virus and rapid progression in a person who has had many high-risk sexual contacts and who used metham-

phetamine. “We cannot conclude if this is due to an aggressive virus or a genetic predisposition”, said Ho. “We do not know if this is a single isolated event or if there are additional cases out there.” The viral sequence is now being compared with those in the database at the Los Alamos National Laboratory, with the hope of finding a closely related HIV-1 strain that might provide an epidemiological linkage to this case. Thus far, the patient does not appear to have any predisposing genetic markers, but testing is still underway.

Roxanne Nelson

Researchers at the New York University School of Medicine (NY, USA) may have found a way to treat latent Kaposi’s sarcoma-associated herpesvirus (KSHV, also known as HHV8) infections. Ornella Flore and colleagues report that glycyrrhizic acid (GA)—a compound isolated from liquorice that inhibits the lytic replication of other herpesviruses—terminates KSHV latent infection of B lymphocytes (J Clin Invest 2005; 115: 642–52). “This is the first time we have found anything that targets latent gene expression in herpesvirus-infected cells”, says Flore, “but it is too soon to say whether GA will be effective against other latent herpesviruses or suitable for clinical use against KSHV”. The treatment of infections caused by herpesvirus is complicated by their ability to establish latent infections. Herpesviruses can hide within their host cells, making only the few proteins needed to maintain latency, and emerges at a later date to cause overt disease. No currently available drugs directly attack latent herpesviruses, although latent Epstein–Barr virus can be reactivated, thus allowing treatment with standard antiviral drugs. http://infection.thelancet.com Vol 5 April 2005

Flore’s team reports that GA disrupts latent KSHV infection of B lymphocytes in culture by downregulating the expression of latency-associated nuclear antigen and upregulating viral cyclin expression, resulting in the selective death of KSHV-infected cells. The next step, explains Flore, “is to see whether GA can inhibit the growth of KSHV-induced human tumours transplanted into mice. GA is already used clinically in Japan to treat hepatitis, so this lead is definitely worth following.” “GA is the first antiviral to have an effect on latently KSHV-infected lymphoma cells”, says KSHV expert Ethel Cesarman (Weill Medical College of Cornell University, New York, USA). But, she notes, “we don’t know yet the sites of KSHV infection in immunocompetent individuals and which (if any) viral genes are expressed, so it is difficult to predict whether GA might clear KSHV completely from the body”. Jindrich Cinatl (University Hospital Medical School, Frankfurt, Germany), who is studying GA treatment of severe acute respiratory syndrome, also finds Flore’s results intriguing. However, he warns that the GA concentrations needed to terminate latent KSHV infec-

ABPL/Sam Stowell

Liquorice compound beats latent herpesvirus

Sweet solution to latent infection?

tion in B lymphocytes are higher than those used to treat hepatitis and may cause unacceptable side-effects. Therefore, chemical modification of GA might be required before it can be used to treat latent herpesvirus infections.

Jane Bradbury 201