Analyses of varicella-zoster virus (VZV) protein expression during latency have been discordant, with rare to many positive neurons detected. We show that ascites-derived murine and rabbit antibodies specific for VZV proteins in vitro contain endogenous antibodies that react with human blood type A antigens in neurons. Apparent VZV neuronal staining and blood type A were strongly associated (by a 2 test, ␣ ؍ 0.0003). Adsorption of ascites-derived monoclonal antibodies or antiserum with type A erythrocytes or the use of in vitro-derived VZV monoclonal antibodies eliminated apparent VZV staining. Animal-derived antibodies must be screened for anti-blood type A reactivity to avoid misidentification of viral proteins in the neurons of the 30 to 40% of individuals who are blood type A. V aricella-zoster virus (VZV) is a human alphaherpesvirus that establishes latency in ganglionic sensory neurons. In autopsied human ganglia, the frequency of individual VZV-positive neurons was 1.0 to 6.9% by single-cell laser capture microdissection (LCMD) and PCR (29). However, immunostaining analyses of VZV protein expression in latently infected neurons have differed significantly. Mahalingam et al. reported infrequent detection of VZV proteins in cadaver ganglia, and in positive tissues VZV protein expression was restricted to very few neurons, a finding confirmed by Kennedy et al. and our recent study (13,16,32). In contrast, Lungu et al. detected VZV proteins in 9 to 24% of neurons in ganglia from three of three subjects (15). Theil et al. found immediate-early 62 (IE62) proteins in ganglia from 38% of individuals and in 3 to 7% of neurons (25). Discrepancies among reports describing the frequencies of VZV protein-positive neurons in autopsied ganglia require further investigation because of their implications for understanding mechanisms of VZV latency.Using a high-potency rabbit anti-IE63 antibody and preimmune serum control, we detected IE63 proteins in ganglia from only 1 of 18 individuals and in Ͻ2.8% of neurons (32). Subsequently, we observed cytoplasmic immunoreactivity in many neurons in ganglia from several individuals when the neurons were stained with monoclonal antibodies (MAbs) to IE62, glycoprotein E (gE), and the capsid protein ORF40 (MAB8616, MAB8612, and MAB8614, respectively; EMD Millipore, Billerica, MA); different lots had similar reactivities. These commercial reagents against IE62 and gE, known to be specific for viral proteins in cultured cells, have been used in studies that report cytoplasmic localization of VZV proteins in neurons (6,9,10,25,26,28). The failure to confirm IE62 and gE detection with other VZV antibodies, the detection of the ORF40 capsid protein detection in latency, and the Golgi zone-like localization of all three VZV proteins suggested a possible staining artifact.The mouse ascites Golgi (MAG) reaction results from endogenous anti-human blood type A antibodies in MAbs derived from mouse ascites (2, 5, 14, 21-23, 30, 31). Importantly, in blood type A individuals, sensory neurons exp...