During inactivation of poliovirus type 1 (PV-1) by exposure to UV, hypochlorite, and heat (72°C), the infectivity of the virus was compared with that of its RNA. DEAE-dextran (1-mg/ml concentration in Dulbecco's modified Eagle medium buffered with 0.05 M Tris, pH 7.4) was used to facilitate transfecting PV-1 RNA into FRhK-4 host cells. After interaction of PV-1 RNA with cell monolayer at room temperature (21 to 22°C) for 20 min, the monolayers were washed with 5 ml of Hanks balanced salt solution. The remainder of the procedure was the same as that for the conventional plaque technique, which was also used for quantifying the PV-1 whole-particle infectivity. Plaque formation by extracted RNA was approximately 100,000-fold less efficient than that by whole virions. The slopes of best-fit regression lines of inactivation curves for virion infectivity and RNA infectivity were compared to determine the target of inactivation. For UV and hypochlorite inactivation the slopes of inactivation curves of virion infectivity and RNA infectivity were not statistically different. However, the difference of slopes of inactivation curves of virion infectivity and RNA infectivity was statistically significant for thermal inactivation. The results of these experiments indicate that viral RNA is a primary target of UV and hypochlorite inactivations but that the sole target of thermal inactivation is the viral capsid.Leading causes of food-borne, and probably water-borne, disease in the United States are the Norwalk-like viruses (NLVs) of the family Caliciviridae and the hepatitis A virus (HAV) of the family Picornaviridae (11). Poliovirus (PV) is the type species of the genus Enterovirus in the Picornaviridae family (19). PV has the same genomic structure and gene organization as that of HAV and has a close phylogenetic relationship with the NLVs (26). We have studied the inactivation of PV, HAV, and feline calicivirus (FCV, which is often used as a surrogate for NLVs because NLVs have no laboratory host cell line). Inactivating agents used in these studies were UV, hypochlorite, and heat (72°C), all of which are commonly used in food processing or preparation and in water disinfection.These simple viruses comprise only a single strand of RNA coated with protein. The RNA contains the genetic information by which intracellular infection results in production of progeny virus, so infectivity ultimately resides in the RNA. The coat protein (capsid) performs three functions: (i) protection of the RNA against environmental degradation and in transit down the digestive tract until susceptible cells are reached; (ii) attachment to the receptor of a susceptible cell, whereby the viral particle is engulfed and the capsid removed, to initiate the infection; and (iii) antigenic activity that evokes an immune response by the host and reacts with the antibody that has been produced. We have shown that capsids of HAV, vaccine PV type 1 (PV-1), and FCV inactivated (from an initial titer of ϳ1,000 PFU/ml) by UV, hypochlorite, or high temperature ...