Intrinsic Cellular Defenses against Human Immunodeficiency Viruses

Abstract

Summary Viral infections are often detrimental to host survival and reproduction. Consequently, hosts have evolved a variety of mechanisms to defend themselves against viruses. A component of this arsenal is a set of proteins, termed restriction factors, which exhibit direct antiviral activity. Among these are several classes of proteins (APOBEC3, TRIM5, Tetherin and SAMHD1) that inhibit the replication of human and simian immunodeficiency viruses. Here, we outline the features, mechanisms, and evolution of these defense mechanisms. We also speculate on how restriction factors arose, how they might interact with the conventional innate and adaptive immune systems and how an understanding of these intrinsic cellular defenses might be usefully exploited.

p53-Derived Host Restriction of HIV-1 Replication by Protein Kinase R-Mediated Tat Phosphorylation and Inactivation

“…HIV-1 infections are detrimental to host survival and reproduction, and hosts have evolved numerous restriction mechanisms to protect themselves from HIV-1 replication (3,45). It has been evidenced that p53 may play an important role in HIV-1 restriction.…”

Rapamycin relieves lentiviral vector transduction resistance in human and mouse hematopoietic stem cells

“…19 Autophagy, a lysosomal degradative pathway that maintains cellular homeostasis and supports survival during periods of stress, is emerging as an antiviral defense mechanism. Autophagy intersects with HIV-1 replication in an intricate manner.…”

SAMHD1 Restricts Herpes Simplex Virus 1 in Macrophages by Limiting DNA Replication

“…Recent years have seen an explosion in the identification of host proteins that act as restriction factors to block specific stages of viral replication cycles in infected cells (2)(3)(4)(5). The antiviral activity of restriction factors can be enhanced by interferons that often upregulate their expression.…”

“…SAMHD1 is implicated as a regulator of the innate immune response, and its expression is induced by interferon (32). The histidine-aspartic acid domain (HD) of the SAMHD1 protein possesses dGTP-reg-ulated deoxynucleotide triphosphohydrolase activity that decreases intracellular deoxynucleotide triphosphate (dNTP) levels (3,33). This activity is responsible for the very low dNTP concentrations found in terminally differentiated nondividing human monocyte-derived macrophages (34,35).…”