Bovine viral diarrhea virus (BVDV) is an economically important pathogen of the livestock industry worldwide. BVDV is classified into cytopathic (cp) and noncytopathic (ncp), depending on its effects on cultured cells. BVDV is known to alter the host's immune response. Of this, major histocompatibility complex (MHC) class II molecules play a central role in the development and function of the immune system, and are comprised of two types, DR and DQ, in cattle. In this study, we investigated the expression of MHC class II on monocytes infected with ncp BVDV1 or ncp BVDV2. Using flow cytometry (P<0.01), mRNA level quantification (quantitative real time RT-PCR, P<0.01), and western blot (P<0.001), we found that the expressions of MHC class IIDQ was significantly decreased in ncp BVDV2-infected monocytes compared with that in ncp BVDV1-infected cells. Furthermore, interferon gamma (IFN) production was markedly decreased in ncp BVDV2-infected monocytes (P<0.001) compared to those with ncp BVDV1 infection. These findings suggest that ncp BVDV2 causes reduced expressions of MHC class II DQ and a decreased production of IFN, resulting in evasion of immune recognition and suppression of the antiviral defense mechanism of the innate immune response. Consequently, the results demonstrate that ncp BVDV1 and ncp BVDV2 interact differently with the host innate immune response. Thus, our data provide insight into the mechanism by which, unlike ncp BVDV1, ncp BVDV2 impairs antigen presentation, fails to control the viral infection, and causes more severe disease.