Three grapevine viruses are considered to pose great threats to grape and wine production in the United States. Those viruses are Grapevine vein clearing virus (GVCV), Grapevine leafroll-associated virus 3 (GLRaV-3) and Grapevine red blotch virus (GRBV). These viruses are prevalent in Missouri vineyards. Even with the threat these viruses pose, research has been done almost exclusively in Vitis vinifera, while little is known about how they might affect the grape hybrids commonly grown in Missouri. In this study we identified 30 grapevines in each hybrid variety of Norton and Chardonel to examine their response to virus infection. We identified 10 Norton vines infected with either GLRaV-3, GRBV, or neither virus in a Norton vineyard, and compared different parameters associated with yield and vine health (cluster counts, individual berry weight, pruning weight), and berry juice quality (Brix, titratable acids (TA), pH). We further identified 10 Chardonel vines infected with GLRaV-3, or a combination of GVCV/GLRaV-3 or GRBV/GLRaV-3 and compared different parameters associated with yield and vine health (cluster counts, individual berry weight, pruning weight), and berry juice quality (Brix, titratable acids (TA), pH). In measuring these parameters for Norton, we found there was no significant difference between berry juice from vines infected with GLRaV-3 and the virus-free vines; however, vines infected with GRBV yielded significantly larger berries and the juice had a higher TA than virus-free samples. We conclude that although Norton is susceptible to both viruses, this host may be tolerant to GLRaV3 infection and may be only moderately affected by GRBV infection. With the Chardonel vines, we examined the effect of GRBV and GVCV in a background infection of GLRaV-3. Surveys of Missouri vineyards have shown that Chardonel is frequently infected with these combinations of viruses. Results showed that vines infected with both GVCV and GLRaV-3 had significant differences in Brix, TA, berry size, and pH from vines infected with only GLRaV-3. By contrast, there were no significant differences between vines infected with both GRBV and GLRaV-3 versus vines infected with only GLRaV-3. In Chardonel we conclude that GVCV can work in synergism with GLRaV-3 to intensify disease, whereas GRBV did not similarly increase any disease effects associated with GLRaV-3. A recent survey for grapevine viruses in Missouri revealed that most of the grape cultivars grown in Missouri vineyards are infected with at least one virus and many grapevines are infected with multiple viruses. The viruses that were detected in the survey have been shown to cause serious problems in Vitis vinifera. However, very few studies have examined the effect of these viruses on the American and French-American cultivars that predominate in Missouri vineyards. To investigate the impact of virus infections on the American and grape hybrids grown in Missouri, we have established a research vineyard at the Mizzou Horticulture and Agroforestry Research Center (HARC) in New Franklin, Missouri, that consists of Norton, Chardonel, and Vidal Blanc vines infected with combinations of up to six viruses found in Missouri vineyards. This research vineyard will allow us to determine how viruses affect the American and French American hybrid grapes that form the basis of the Missouri grape and wine industry.