Posted on August 11, 2014
Source: Diego A. Espinoza
This summer, I am working in the laboratory of Dr. Kenneth W. Witwer in the Retrovirus Laboratory at the Johns Hopkins University School of Medicine. The Retrovirus Laboratory uses an animal model to better understand human HIV infection, particularly HIV’s role in central nervous system, pulmonary, and cardiac disease. The animal model we use is the SIV/macaque model: SIV (simian immunodeficiency virus) is the “monkey form” of HIV, and macaques are a type of monkey that can be infected by SIV. This animal model has proven to be an effective model of HIV infection in humans.
Dr. Witwer’s group focuses on the role of microRNAs (miRNAs) in HIV infection, and thus my project for the summer has been to work on identifying the role of miRNAs in SIV infection of rhesus macaque astrocytes.
What is SIV? What are rhesus macaques? What are astrocytes? What are miRNAs? What is the purpose of studying these things?
SIV is the “monkey form” of HIV. It behaves very similar to HIV, except it infects monkeys rather than humans. It is predicted that at some point in history, HIV came to be when SIV somehow mutated and infected human beings.
The Rhesus macaque is a type of monkey that can be infected by SIV. These monkeys, when infected with SIV, have been shown to make an excellent model for HIV infection in humans.
Astrocytes are a type of cell in the central nervous system (CNS). They are the most abundant type of cell in the human brain, and are also present in rhesus macaque brains. They have been shown to be susceptible to HIV infection (in humans) and SIV infection (in rhesus macaques). They are “helper” cells in a way – they help the brain and spinal cord with all sorts of functions, and also help combat infection in the CNS.
miRNAs are small strands of RNA that are present inside of cells (like astrocytes) and sometimes outside of cells . These strands can bind to messenger RNAs (mRNAs) inside cells and degrade them – preventing them from making proteins as intended, and effectively silencing these mRNAs or lowering their expression, altering certain cellular processes. By studying the levels of miRNAs in cells, one can gain a better picture of the regulatory processes that are going on inside the cells. Usually cells make their own miRNAs, but there is evidence that viruses might be able to produce miRNAs inside their host cells.
My project aims to look at the role of miRNAs inside SIV-infected rhesus macaque astrocytes. Could this infection of SIV trigger some cellular response inside the astrocytes that causes a change in the levels of certain miRNAs? Are these miRNAs involved in any particular cell process that is linked to controlling infection? Is it possible that SIV is infecting astrocytes and making its own miRNAs inside of them, and if so, how do these miRNAs affect the cells?
So, why does this all even matter?
There are quite a few reasons behind this research. One in particular, is to better understand HIV-associated neurocognitive disorders. Many HIV patients experience a form of neurocognitive disorders caused by the infection of the CNS by HIV. These disorders can range from impaired motor function to dementia, among others. By looking at the processes occurring inside SIV infected astrocytes, we can hope to get clues as to what is occurring in the brain during infection, and how we can potentially treat or prevent these disorders.
Another reason to look at astrocytes is because of the possibility of the presence of viral reservoirs in the CNS. Viral reservoirs are locations (tissues or cells) in the body where HIV is theorized to “hide” during treatment. When an HIV-infected person undergoes modern treatment, their viral loads can reach “undetectable” amounts in the blood. However, if the treatment stops, the person will shortly show a rebound in the amount of virus in their blood, back up to significantly detectable levels. It is predicted that this rebound is caused by the presence of viral reservoirs: once treatment stops, the viral reservoirs are able to release more virus into the blood. If one hopes to find a cure for HIV, the theory is that these viral reservoirs must be eliminated. The CNS is a predicted location of viral reservoirs, which is why understanding SIV infection in astrocytes can help us understand how the virus may be able to survive in the CNS. Hopefully, this research will help scientists learn more about HIV, and ultimately, help in the fight to find a cure.
