Anti-HIV Factors: Targeting Each Step of HIV's Replication Cycle

Curr HIV Res. 2016;14(3):175-82. doi: 10.2174/1570162x14999160224094621.

Abstract

Background: Similar to other animal viruses, HIV-1 relies on the contributions of the cellular machinery to ensure efficient virus propagation. However, human cells have evolved refined mechanisms to block key steps of the virus life-cycle, thereby suppressing viral replication. These cellular proteins are generally known as restriction factors, and they provide an early antiviral defense. So far, five potent restriction factors have been shown to effectively block HIV and/or SIV replication. These are TRIM5 proteins, SAMHD-1, members of the APOBEC3 (A3) family, Mx2 and Tetherin/BST-2.

Results: Here, we review the antiviral mechanisms of these and other antiviral factors, their interaction with the innate immune responses, and how their functions might be exploited to clear and prevent HIV infection.

Conclusion: Since the majority of vaccine approaches against HIV have failed so far, it is imperative to start looking at alternative strategies for vaccine and therapy development. By better understanding how HIV hijacks the cellular machinery for its own benefit in completing its life-cycle, and how the virus adapts to circumvent our intrinsic immunity, we will be better equipped to design compounds that specifically interrupt virus replication and spread.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • APOBEC-3G Deaminase / metabolism
  • Animals
  • Antigens, CD / metabolism
  • Antiviral Restriction Factors
  • Carrier Proteins / metabolism
  • GPI-Linked Proteins / metabolism
  • HIV Infections / etiology*
  • HIV Infections / metabolism*
  • HIV-1 / physiology*
  • Host-Pathogen Interactions*
  • Humans
  • Monomeric GTP-Binding Proteins / metabolism
  • Myxovirus Resistance Proteins / metabolism
  • SAM Domain and HD Domain-Containing Protein 1
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / metabolism
  • Virus Replication*

Substances

  • Antigens, CD
  • Antiviral Restriction Factors
  • BST2 protein, human
  • Carrier Proteins
  • GPI-Linked Proteins
  • MX2 protein, human
  • Myxovirus Resistance Proteins
  • Tripartite Motif Proteins
  • RNF115 protein, human
  • TRIM5 protein, human
  • Ubiquitin-Protein Ligases
  • SAM Domain and HD Domain-Containing Protein 1
  • SAMHD1 protein, human
  • APOBEC-3G Deaminase
  • Monomeric GTP-Binding Proteins