Much research and development goes into figuring out treatment and vaccine options for the HIV-1 virus as the AIDS pandemic spreads globally. Many approaches aim to stop retroviral replication, many investing in the antisense strategy focusing on polyamide nucleic acids.The transactivator responsive region (TAR) of the HIV-1 genome has recently been discovered as a possible target of antiretroviral medication. FACScan analysis of the efficiency of cellular uptake of conjugated MTD peptides, penetratin, tat peptide, transportan-27, and two truncated derivatives of transportan-21 and transportan-22, to a 16mer PNA targeted to the TAR region showed that uptake was concentration dependent. Interestingly it also revealed PNA TAR penetratin congugate was most efficient with MTD. This leads researchers to believe that anti-HIV-1 PNA in conjugate with MTD peptides inhibit HIV-1 in vitro replication and could also reduce HIV-1 infectivity.
Tripathi S. et al. Anti-HIV-1 activity of anti-TAR polyamide nucleic acid conjugated with various membrane transducing peptides. 2005 Aug 2;33(13):4345-56. Print 2005.
Retroviruses have been studied for their possible anti-cancer properties. Inhibition of tumor angiogenesis relies on the inhibition of the neovasculature. In this study, a vascular endothlial growth factor receptor-2 (sFLK-2) was mediated by retrovirus and seen to inhibit tumorgenicity in genes S180, MCF-7, and B16 live cells. This is a big step in using retrovirus mediated therapy as anti cancer therapy and plays a big role in anti cancer treatment development.
Kou B. et al. Gene therapeutic exploration: retrovirus-mediated soluble vascular endothelial growth factor receptor-2 (sFLK-1) inhibits the tumorigenicity of S180, MCF-7, and B16 cells in vivo. Oncol Res. 2005;15(5):239-47.
A high viral load of HIV-1 virus in the cerebrospinal fluid can lead to neurological symptoms in infected patients. While the Central Nervous System is not typically a "sanctuary site" 39% of HIV-1 infected patients displayed neurological symptoms. In this recent study, researchers demonstrated that antiretroviral therapy directly injected into the cerebralspinal fluid can have a therepeutic effect on patients experiencing symptoms.
Mellgren A. et al. Cerebrospinal fluid HIV-1 infection usually responds well to antiretroviral treatment. Antivir Ther. 2005;10(6):701-7.
HIV-1 initially uses CCR5 receptors to gain entry into the cell; however natural evolution results in a switch to CXCR4 usage, which is associated with expanded target cell range and worsened cell prognosis. Why this switch takes so long is puzzling because it only takes one to two mutations to occur. Scientists investigated potential obstacles to CCR5-CXCR4 switching. It was determined that a diminished replication fitness, less-efficient co-receptor use, and unique mutational pathways have been suggested as reasons why CXCR4-using viruses take so long to emerge.
Pastore et al. Intrinsic Obstacles to Human Immunodeficiency Virus Type 1 Coreceptor Switching. Journal of Virology. 2004; 78:7565-74.