Abstract
Human immunodeficiency virus-1 (HIV-1) dynamics reflect an intricate balance within the viruses’ host. The virus relies on host replication factors, but must escape or counter its host’s antiviral restriction factors. The interaction between the HIV-1 protein Vif and many cellular restriction factors from the APOBEC3 protein family is a prominent example of this evolutionary arms race. The viral infectivity factor (Vif) protein largely neutralizes APOBEC3 proteins, which can induce in vivo hypermutations in HIV-1 to the extent of lethal mutagenesis, and ensures the production of viable virus particles. HIV-1 also uses the APOBEC3-Vif interaction to modulate its own mutation rate in harsh or variable environments, and it is a model of adaptation in a coevolutionary setting. Both experimental evidence and the substantiation of the underlying dynamics through coevolutionary models are presented as complementary views of a coevolutionary arms race.
Highlights
After the early years of the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)-epidemic, monotherapy with the first antiretroviral active drug azidothymidine (AZT, licensed 1987) was enthusiastically embraced [1]
Human immunodeficiency virus-1 (HIV-1)’s ability to replicate in the presence of A3F/G strictly relies on the viral infectivity factor (Vif) protein as described above
This study showed that hypermutated HIV-1 generated replication-competent drug resistant viruses only through recombination with wt HIV-1 [123]
Summary
After the early years of the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)-epidemic, monotherapy with the first antiretroviral active drug azidothymidine (AZT, licensed 1987) was enthusiastically embraced [1]. The most prominent examples of HIV-1 restriction factors are APOBEC3G, TRIM5α, Tetherin and SAMHD1 [13,14] These proteins are either constitutively expressed or induced by interferons and act in a non-secreted way directly to inhibit specific steps of the viral replication cycle in either virus producer or virus target cells. It appears that the main task of some HIV accessory proteins is to counteract cellular restriction factors. While in HIV-1 no protein evolved to inhibit SAMHD1, the related HIV-2 uses its Vpx protein to destroy this dNTPase [15,16,17]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call