From the last issue, a current controversy about the mutant H5N1 was discussed. I will continue the discussion by talking about some essential aspects of deriving successful mutants. These mutants can have completely different tropism for tissues or animals. The understanding by how a mutant is derived had recently stirred a debate between academic freedom and bioterrorism. Personally, I think the understanding of how to derive mutants is crucial in aiding us to define how new viruses are evolved.
Receptor influences viral entry
Binding to the cellular receptor is the first step when the virus comes in contact with the host cell. The cells that express a particular type of receptor make them susceptible to viral infection. Other than the susceptibility, one must also consider if cells have the required machinery for a productive infectious cycle. This is what defined the term, permissive. Here, I will discuss a paper from Higgs’ lab at the University of Texas, called a single mutation in Chikungunya (CHIKV) virus affects vector specificity and epidemic potential (shown right).
The CHIKV strain that circulates in 2005-2006 epidemic on Reunion island is different from normal CHIKV infection. This particular strain is not transmitted through the normal route: Aedes aegypti (which is the same species responsible for dengue viral infection in human). In fact, it is transmitted by the Asian tiger mosquito called Ae. albopictus. By sequencing, these researchers found a particular mutation at the E1 protein at the site 226 (mutated from Alanine to Valine).
Interestingly, when they look at the replication of both strains within the same organism, they found that the 226V mutant is more successful in replicating within the Ae. albopictus but not at the Ae. aegypti.
They also supported this result by looking at the dissemination of each strain. It is clear that the 226V mutant is more successful in completing the infectious cycle against 226A mutant only in Ae. albopictus. In contrast, 226V mutant does not have an advantage in Ae. aegypti. The researchers then went on to support the conclusion by infecting animals with the mosquitoes.
E1 is a part of the spike on the CHIKV envelope. Complexed with E2 in the hetero-trimeric spike structure, this complex facilitates the interaction with cellular receptor, entry, and budding. The mutation in E1 protein can completely change the tropism for its vector. It is also able to compete against wildtype viruses. The bottom line is the change in viral envelope proteins can change its preference of cells that it can infect. In other words, envelope proteins must be mutated in a way that it can recognize cells that express different receptors.
PLoS Pathog. 2007 Dec;3(12):e201.
A single mutation in chikungunya virus affects vector specificity and epidemic potential.