Post-entry Restrictions to Lentiviral Replication
Jenny L Anderson and Gilda Tachedjian
from: Lentiviruses and Macrophages: Molecular and Cellular Interactions (Edited by: Moira Desport). Caister Academic Press, U.K. (2010)
Host organisms contain numerous defenses to protect themselves against invading pathogens like lentiviruses. These defense systems include intracellular inhibitory proteins termed "restriction factors", which have recently risen to prominence with the discovery of APOBEC3 and TRIM5 cellular proteins as key factors restricting invading retroviruses in host cells. Understanding how these and other intracellular restriction factors block retroviruses is providing new insights into barriers of retroviral replication and the cross-species transmission of lentiviruses. Moreover, these restriction factors have important ramifications for identifying new targets for antiviral therapy, developing better models of HIV-1/AIDS and selecting retroviral vectors for gene therapy. Thus, restriction factors have emerged as a dynamic, important area of lentivirus research. This chapter reviews rapid advances in understanding intracellular restriction factors targeting retroviruses after entry into host cells. These restriction factors include TRIM5α, TRIMCyp, Cyclophilin A, Fv1, APOBEC3, TRIM28, ZAP, tetherin and calcium-modulating cyclophilin ligand. Lentiviral countermeasures to circumvent these intracellular restrictions are also canvassed. Delineating the biology of these intracellular restrictions appears promising for developing novel antiviral therapies to curb lentiviruses as effectively as the naturally occurring intracellular restriction factors read more ...