Many viral infections occupy organs and tissues throughout the body, but in vivo assessments frequently estimate viral loads based on plasma samples or select tissue biopsies. These indirect measurements can guide clinical management of systemic infections, but they might inaccurately represent the distribution and intensity of virus replication in different tissues. Once an infection is successfully subdued, these common measurements can yield negative results for viral presence while replication and evolution still occur in un-monitored viral reservoirs.

Modern techniques in medical imaging now permit researchers to monitor systemic conditions on a large, even whole-body scale. In combination with antibody therapy, positron emission tomography (PET) scans can provide repeatable, in vivo visualizations of radioactively labeled features. When targeting a virus, immunoPET methods can help detect, localize and monitor systemic infection across multiple tissues over time.

To this end, researchers lead by Francois Villinger (Emory University, Atlanta, GA) developed an immunoPET probe that targets the simian immunodeficiency virus (SIV) in infected rhesus macaques, which closely model humans with SIV's human cognate, HIV. Villinger's team joined a detectable radiotracer to antibodies that target the glycoprotein Gp120, which occurs on the surface of the viral envelope of SIV. They then introduced this antibody to chronically infected macaques and to 'elite controllers'—individuals that are infected but naturally manage the virus below detectable levels without treatment (Nat. Methods doi:10.1038/nmeth.3320; published online 9 March 2015). Using immunoPET, they tracked the uptake of this antibody in different tissues and compared the localization of infected tissues between control macaques, elite controllers and chronically infected macaques (before and during anti-retroviral therapy).

Among the expected results, the authors were surprised to find discrete areas of virus replication in nasal tissues and the male reproductive tract of macaques, even after anti-retroviral therapy. These reservoirs are important both because they were unanticipated and because they are otherwise difficult to sample in live animals.

These new findings emphasize the need for care and caution when interpreting biopsies and plasma samples, as these measurements can inaccurately represent the virus load across different tissues. The authors anticipate that this methodology should be translatable to humans, where it could reveal how infection takes hold and lingers, dormant, during successful repression. It might even inform site-specific treatments to eradicate such reservoirs and prevent reactivation of successfully managed infections.