Key reports from the 9th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 2007.

The 9th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV provided a forum for the presentation of basic and clinical research focused on the pathogenesis and management of lipodystrophy and other adverse events associated with antiretroviral therapy. New data were reported on the contribution of both antiretroviral therapy and HIV infection itself on the development of metabolic abnormalities in patients with lipodystrophy, including insulin resistance and dyslipidaemia, which are associated with an increased risk of diabetes and cardiovascular disease. In addition, an emerging role of HIV and antiretroviral therapy in bone, liver and kidney disease were highlighted. A major focus of the data presented in these areas concerned the identification and evaluation of risk factors and appropriate surrogate markers for defining cardiovascular disease risk as well as other outcomes of long-term treatment. The complexity of defining such risk factors was underscored by data describing the impact of race, age and gender in the progression of metabolic disease and related complications among different HIV-infected populations. Finally, advances in the development of pharmacovigilance reporting systems in resource-limited settings and their impact upon healthcare policies and the provision of patient care were also described.

Characterization of infectious Murray Valley encephalitis virus derived from a stably cloned genome-length cDNA.

An infectious cDNA clone of Murray Valley encephalitis virus prototype strain 1-51 (MVE-1-51) was constructed by stably inserting genome-length cDNA into the low-copy-number plasmid vector pMC18. Designated pMVE-1-51, the clone consisted of genome-length cDNA of MVE-1-51 under the control of a T7 RNA polymerase promoter. The clone was constructed by using existing components of a cDNA library, in addition to cDNA of the 3' terminus derived by RT-PCR of poly(A)-tailed viral RNA. Upon comparison with other flavivirus sequences, the previously undetermined sequence of the 3' UTR was found to contain elements conserved throughout the genus FLAVIVIRUS: RNA transcribed from pMVE-1-51 and subsequently transfected into BHK-21 cells generated infectious virus. The plaque morphology, replication kinetics and antigenic profile of clone-derived virus (CDV-1-51) was similar to the parental virus in vitro. Furthermore, the virulence properties of CDV-1-51 and MVE-1-51 (LD(50) values and mortality profiles) were found to be identical in vivo in the mouse model. Through site-directed mutagenesis, the infectious clone should serve as a valuable tool for investigating the molecular determinants of virulence in MVE virus.