Background
Human immunodeficiency virus (HIV) is the result of the cross-species transmission of simian immunodeficiency viruses (SIVs) that endemically infect non-human primates. While pandemic HIV-1 M is the result of a chimpanzee lentivirus (SIVcpz) cross-species transmission to humans, lentiviruses from other non-human primates have also spilled over into humans. Since the emergence of HIV, the field has sought to characterize the cell-intrinsic determinants of primate lentivirus cross-species transmission. However, the factors that enable lentivirus zoonosis are not completely understood.
Methods
Our lab developed a high-throughput HIV-CRISPR screen to unveil cell-intrinsic proviral and antiviral factors in the context of HIV infection. The approach involves a uniquely engineered sgRNA and Cas9 vector which allows for packaging of the sgRNA sequence from progenitor cells. We are now implementing the HIV-CRISPR screening methodology to reveal barriers specific to pre-pandemic lentiviruses, such as SIVcpz, in human cells.
Results
We have screened 3 genetically diverse SIVcpz viruses using a genome-wide sgRNA library in THP-1 cells. Among our hits are genes involved in the tethering of virions at the cell surface and the inhibition of broadly important transcriptional machinery for lentiviral replication.
Conclusions
Our unbiased screening approach will help us better define the evolutionary barriers of SIV infection in human cells. We aim to identify key host factors that may underlie the evolutionary origins of HIV.
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