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John A. T. Young

 

John A. T. Young

John A. T. Young

Professor
Immunobiology and Microbial Pathogenesis Laboratory

"One of the major long-term goals of the work in our lab is to uncover the repertoire of cellular factors involved in early replication steps of viruses such as HIV, the cause of AIDS. Identification and characterization of these factors provides brand-new insights into the cell biology of HIV infections and could suggest new therapeutic approaches for the treatment of AIDS."

Recent studies have come to the sobering conclusion that HIV remains "hidden" in a latent form, even after long-term suppression with highly active antiretroviral therapy. Moreover, viral drug resistance represents a formidable problem, creating an urgent need for new classes of antiretrovirals aimed at preventing infections rather than merely keeping them in check.

Young and a team of collaborators recently combined several layers of genomewide analyses to identify cellular proteins that give the AIDS virus a helping hand during the early stages of infection. Taking advantage of short-interfering RNA (siRNA) technology—bits of genetic code that silence cellular gene expression, one gene at a time, when introduced into a cell—the initial screen examined more than 144,000 siRNAs for their effects on HIV-1 infection, yielding several thousand hits. Team members then combined the data with information from protein-protein interaction databases and sifted through the results to determine when in the virus's life cycle the proteins' help was needed. They identified clusters of interacting proteins that affect discrete steps in the early stages of HIV infection, such as entering host cells, shedding the viral RNA's protective coat, copying the RNA into DNA—a process known as reverse transcription— crossing into the nucleus, and finding a suitable spot in the host's genome to permanently move into.

An in-depth, genomewide host-pathogen interaction analysis then allowed researchers to group the host factors according to their interactions with each other and viral proteins, as well as their role during the virus's lifecycle. The process revealed cellular proteins that, when lacking, merely slow the virus down—a fact missed by earlier screens. This group of genes may be particularly important in vivo since the virus is racing its host; the sooner it can get in, copy itself, and get out, the better for the virus.

The new roster of just over 200 host cofactors this study has produced raises the prospect of novel therapeutic targets for HIV, and Young and his team are now following up, trying to find potential targets for drug development.

Lab Photo

Left to right:
Suchita Bhattacharyya, Shilpi Sharma, John Marlett, Rose Pilpa, John Young, Melissa Rodgers, Shannon Seidel, John Naughton, Patti Ryan, Brooke Baker

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John A. T. Young

Faculty

John A. T. Young

John A. T. Young

Professor
Immunobiology and Microbial Pathogenesis Laboratory

John A. T. Young, a Professor in the Infectious Disease Laboratory, studies the cell biology of virus infection and anthrax intoxication. His laboratory is identifying and characterizing cellular factors that contribute to the early steps of infection by HIV and other retroviruses, influenza virus, and filoviruses such as Ebola virus. These studies are giving novel insights into virus-host interactions and are suggesting new therapeutic strategies for combating virus infection. The Young laboratory has also identified both known cellular receptors for anthrax toxin. Current research in the lab is aimed at understanding how these receptors, along with other cellular factors, regulate anthrax toxin entry into cells. Soluble versions of a cellular receptor are also being developed as receptor decoys to efficiently neutralize anthrax toxin.

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