Recurrent Loss of APOBEC3H Activity during Primate Evolution.

Area of Science:

• Genetics
• Evolutionary Biology
• Virology

Background:

• The APOBEC3 family of genes provides antiviral defense by encoding cytidine deaminases.
• APOBEC3H (A3H) is highly polymorphic in humans, with variations affecting protein stability, antiviral activity, and interaction with viral factors like Vif.
• Vif counteracts A3H through proteasomal degradation, influencing lentiviral adaptation.

Purpose of the Study:

• To investigate the evolution and variation of A3H in African green monkeys (AGMs) to understand A3H-Vif interactions and A3H evolution in Old World monkeys.
• To determine the factors contributing to the loss of A3H antiviral activity in primates.

Main Methods:

• Characterization of A3H genetic variation across four AGM subspecies.
• Analysis of A3H protein stability, expression levels, and functional activity.
• Investigation of evolutionary pressures on A3H, including Vif interactions.

Main Results:

• A3H is highly polymorphic in AGMs, with multiple instances of lost antiviral activity.
• Loss of A3H function is linked to reduced protein expression and N-terminal amino acid mutations.
• Evidence suggests Vif did not drive A3H evolution in primate lineages leading to AGMs.

Conclusions:

• APOBEC3H activity is evolutionarily dynamic, with recurrent losses observed in primates.
• The loss of A3H function may be driven by a negative impact on host fitness.
• Differential selective pressures on APOBEC3 genes contribute to primate-specific viral adaptations.