Abstract
The ubiquitin-proteasome system (UPS) ensures regulation of the protein pool in the cell by ubiquitination of proteins followed by their degradation by the proteasome. It plays a central role in the cell under normal physiological conditions as well as during viral infections. On the one hand, the UPS can be used by the cell to degrade viral proteins, thereby restricting the viral infection. On the other hand, it can also be subverted by the virus to its own advantage, notably to induce degradation of cellular restriction factors. This makes the UPS a central player in viral restriction and counter-restriction. In this respect, the human immunodeficiency viruses (HIV-1 and 2) represent excellent examples. Indeed, many steps of the HIV life cycle are restricted by cellular proteins, some of which are themselves components of the UPS. However, HIV itself hijacks the UPS to mediate defense against several cellular restriction factors. For example, the HIV auxiliary proteins Vif, Vpx and Vpu counteract specific restriction factors by the recruitment of cellular UPS components. In this review, we describe the interplay between HIV and the UPS to illustrate its role in the restriction of viral infections and its hijacking by viral proteins for counter-restriction.
Highlights
The human cell is in a continuous arms race with various viruses
The ubiquitin-proteasome system (UPS) plays an important role in viral infections in general and especially in the process of viral restriction and counter-restriction
Several HIV auxiliary proteins have evolved the ability to interact with components of the UPS, subverting it for its own means
Summary
The human cell is in a continuous arms race with various viruses This has led to the coevolution of cellular restriction factors on the one hand and viral proteins for counter-defense on the other hand. Restriction factors are generally induced as a result of an interferon response—they use unique mechanisms to impair specific steps of the replication cycle and they exhibit a dominant and autonomous effect. In this continuous fight, the ubiquitin-proteasome system (UPS) plays a central role on the cellular as well as on the viral side. We will describe the mechanisms by which the human immunodeficiency viruses (HIV-1 and 2) use and subvert the UPS in the continuous battle between cellular defense and viral counter-defense
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