Role of the SKIP complex in HIV-1 Tat transactivation
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Human immunodeficiency virus (HIV) is the etiological agent of Acquired Immune Deficiency Syndrome (AIDS). The virus gradually disrupts the immune system of infected individuals over the years by killing essential immune cells such as T-cells, which are the gatekeepers of our effective immune system. HIV destroys the immune system’s memory as well. As HIV levels increase the groups of T-cells programmed to recognize infections become depleted. This is why HIV-infected people are more susceptible for infections and illnesses. The major obstacle in fighting against HIV is that the virus constantly changes itself to avoid attack by the antibodies and immune cells that normally control infections. This also means that HIV can rapidly become resistant against drug medication targeted for viral proteins, too. Therefore new strategies are needed to inhibit HIV replication. One way can be that specific cellular proteins would be targeted by drugs, which is required for HIV replication. The advantage of this strategy is that the cellular proteins are much less changeable in contrast to the viral proteins, thus they will likely not become resistant against HIV-specific drugs. It is known that the efficiency of HIV replication depends on the expression of the viral genes. If we could block the expression of viral genes, the replication of HIV would be abrogated. In the regulation of HIV gene expression several cellular proteins are involved whose core components are known but their associated constituents and their function in HIV gene expression are largely unknown. There are research data indicating that inhibition of these cellular factors leads to the block of viral growth. In my research proposal I am going to study a cellular protein, called SKIP, required for the expression of HIV genes. The research work will be performed in the laboratory at the Salk Institute where this protein has been discovered to be involved in HIV gene expression. It is still unknown how SKIP functions in this process and contributes to the pathogenesis of HIV. To gain insight into its function my first aim is to purify and identify the SKIP-associated cellular proteins, which are presumably necessary for SKIP to regulate the expression of HIV genes. I will test the identified proteins in several HIV-specific biochemical assays established in the host laboratory. Since the host laboratory is experienced in the molecular biology of HIV, which has discovered several cellular key proteins involved in the regulation of HIV gene expression, I can get an excellent training in the molecular biology of HIV in this laboratory. It is worthy of note that SKIP and several of the other cellular proteins involved in the regulation of the expression of HIV genes are also implicated in the control of the gene expression of other human pathogenic viruses such as human cytomegalovirus and Epstein-Barr virus. Therefore, understanding of the mechanism of how these specific cellular proteins can control the expression of HIV and cellular genes may give us deeper understanding of viral pathogenesis in general.