Innate immune surveillance of the circulation: A review on the removal of circulating virions from the bloodstream

Many viruses utilize the lymphohematogenous route for dissemination; however, they may not freely use this highway unchecked. The reticuloendothelial system (RES) is an innate defense system that surveys circulating blood, recognizing and capturing viral particles. Examination of the literature shows that the bulk of viral clearance is mediated by the liver; however, the precise mechanism(s) mediating viral vascular clearance vary between viruses and, in many cases, remains poorly defined. Herein, we summarize what is known regarding the recognition and capture of virions from the circulation prior to the generation of a specific antibody response. We also discuss the consequences of viral capture on viral pathogenesis and the fate of the captor cell. Finally, this understudied topic has implications beyond viral pathogenesis, including effects on arbovirus ecology and the application of virus-vectored gene therapies.

Author summary
Limiting the amount of virus freely circulating in the bloodstream can be important for controlling viral pathogenesis and transmission. However, despite early advances, this field of study has become overlooked and understudied. Innate immune cells in the liver and spleen constantly survey and remove from circulation viral particles without the aid of virus-specific antibody. The details of these host–virus interactions, and the consequences thereof, remain unknown for many viruses. Yet, understanding this phenomenon has implications not only on bettering our understanding of disease progress, but also on arbovirus ecology and the development of effective virus-vectored gene therapies.