Abstract
A recessive genetic screen of an insertionally mutated Blm-/- ES cell library identifies host factors required for retroviral infection, and confirms that mCat-1 is the ecotropic murine leukaemia virus receptor in ES cells.
Highlights
Host factors required for retroviral infection are potential targets for the modulation of diseases caused by retroviruses
Evidence of the importance of host factors is provided by individuals who harbor homozygous mutations in the gene encoding CC chemokine receptor (CCR)5, who are extremely resistant to HIV infection
Infected cells expressing the puro-Δtk fusion gene are sensitive to 1-(-2-deoxy-2-fluoro-1-β-D-arabino-furanosyl)-5iodouracil (FIAU) negative selection; mutant embryonic stem (ES) cells that cannot be infected by the virus will survive this negative selection
Summary
Host factors required for retroviral infection are potential targets for the modulation of diseases caused by retroviruses. During the retroviral life cycle, numerous cellular factors interact with the virus and play an essential role in infection. Study of the host factors that are involved in the retroviral life cycle is important if we are to gain a detailed understanding of the interaction between virus and host cell components. Many viruses have small genomes, and so the repertoire of components that can be exploited as pharmaceutical targets is very limited. Because of their rapid replication, variants in the viral genome that overcome the effect of inhibitors will be rapidly selected, diminishing the effectiveness of antiviral agents. As a result of these observations, human antibodies to CCR5 and small-molecule CCR5 antagonists are being investigated as potential HIV therapies [1,4]
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