In contrast to a prior study of SIV Nef isolates that reported a correlation between SERINC5 antagonism activity and prevalence of SIV strains in wild primates [27], our results indicate that Nef’s ability to counteract SERINC5 (or SERINC3) does not obviously correlate with global HIV subtype prevalence: indeed, subtype C accounts for nearly 50% of all HIV infections worldwide [21], yet subtype C Nef clones displayed lower median SERINC5 internalization function compared to those from subtypes B and D in our assays. The gene discussed is SERINC3; the disease is HIV infectious disease.