Retrovirus-Based Surrogate Systems for BSL-2 High-Throughput Screening of Antivirals Targeting BSL-3/4 Hemorrhagic Fever-Causing Viruses.

The majority of viruses causing hemorrhagic fever in humans are Risk Group 3 or 4 pathogens and, therefore, can only be handled in biosafety level 3 or 4 (BSL-3/4) containment laboratories. The restricted number of such laboratories, the substantial financial requirements to maintain them, and safety concerns for the laboratory workers pose formidable challenges for rapid medical countermeasure discovery and evaluation. BSL-2 surrogate systems are a less challenging, cheap, and fast alternative to the use of live high-consequence viruses for dissecting and targeting individual steps of viral lifecycles with a diminished threat to the laboratory worker. Typical surrogate systems are virion-like particles (VLPs), transcriptionally active ("infectious") VLPs, minigenome systems, recombinant heterotypic viruses encoding proteins of target viruses, and vesiculoviral or retroviral pseudotype systems. Here, we outline the use of retroviral pseudotypes for identification of antivirals against BSL-4 pathogens.