Some viruses appear to know how to cut proteins responsible for generating immune responses.
Researchers at the U.S. Naval Research Laboratory (NRL) have identified viral proteases from positive-sense single-stranded RNA viruses that cut host proteins involved in the generation of immediate, immune responses to the viruses. The viruses use a "search and delete" algorithm to target and destroy the host proteins.
The procedures created by the scientists to emulate this virus behavior depict how the viruses edit host proteomes –– a process that is similar to the one employed by the CRISPR-Cas9 system, which is widely used for gene-editing, to destroy invading strands of phage DNA.
The determined that the virus proteases use a targeted strategy to cleave specific sites in proteins related to immunity, which allows the viruses to replicate. The scientists call the target host protein sequences short stretches of homologous host-pathogen protein sequences (SSHHPS) as a way to acknowledge the NRL.
For the Zika virus, the target sequences were found in FOXG1, NT5M and SFRP1 proteins, which are involved in brain and eye development. Infection of pregnant women with the virus can lead to the birth of babies with microcephaly, an unusually small head size.
Perhaps most importantly, the algorithm can be used by scientists to understand human antiviral defense systems, to potentially predict how the virus will affect the host and to possibly identify animal models for antiviral drug development by finding animals with the same targeted proteins. Specifically, with the algorithm, researchers can compare protein sequences attacked by a virus in the human body with databases of animal proteins to find matching sequences.
For instance, the researchers discovered that horses, which are killed by the Venezuelan equine encephalitis virus, lack part of an immune response protein present in humans that enables the human immune system to fight the virus.
The scientists have developed software to perform the algorithm, eliminating the need to make tables of protein sequences by hand.