Characterization of HIV-1 surface proteins

Background

The Human Immunodeficiency Virus (HIV)/ Acquired Immunodeficiency Syndrome (AIDS) remains one of the worst pandemics in human history. Over the past three decades, various studies have taken initiative towards finding a cure for AIDS. While a number of anti-retrovirus drugs have been developed to increase the life span of HIV infected individuals, millions of people are still struggling with the disease and its side effects. A preventative approach, such as a strong HIV vaccine, could prevent the spread of the virus. Recently the surface proteins of HIV, collectively known as envelop proteins, or Env, have generated promising results by their ability to increase the reactivity of the immune system cells; a process vital for eradicating the virus from the body. However, HIV-1 Env is highly dynamic and has high mutation rates, making vaccine design extremely challenging.

Proteome Imaging of Macromolecular Systems

The Env protein is consistent of three double-units, also known as dimers, comprised of virus bound gp41 and extended arms, gp120, which through a sequence of responsive changes, allow the entry of HIV into the host human cells. On the surface of the virus, Env is assembled in a fan-like shape trimer. A soluble form of Env, gp140 is a candidate for vaccine design. Therefore, structural characterization of gp140 is a crucial step in designing an immunogen-based vaccine.

Using high resolution transmission cryo-electron microscopy techniques, the PIOMS team has made breakthroughs in generating high resolution 3D structures of gp145. Our team has taken careful steps in analyzing 2-dimensional cryo-electron microscopy films, and selecting representative projections of the purified gp145 proteins. Subsequently, through a combination of human and computer algorithms, these projections have been compiled into high resolution 3D images; based on which critical biochemical and structural information can be obtained – ultimately increasing our understanding of the nature and function of HIV Env.

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Shawyon Malek has been with the PIOMS team and UC Davis Cheng Lab since 2012. His research is focused on structural characterization of HIV Env, gp145, as well as vaccine design against HIV.