Newcastle disease virus is a member of family Paramyxoviridae that infects chicken. Its genome comprises ~15.2 kb negative-sense RNA that encodes six major proteins. The virus encodes various proteins; among all, nucleocapsid (NP) and matrix (M) help in virus replication and its budding from the host cells, respectively. In this study, we investigated the intracellular distribution of NP and M upon expression in the yeast Saccharomyces cerevisiae. We observed nuclear targeting of M, and vacuolar localization of NP was observed in a fraction of yeast cells. Prolonged expression of GFP fused NP or M resulted in altered cell viability and intracellular production of reactive oxygen species in yeast cells. The expression of viral proteins did not alter the morphology and number of the organelles such as nucleus, mitochondria, endoplasmic reticulum, and peroxisomes. However, a significant effect was observed on vacuolar morphology and number in yeast cells. These observations point towards the importance of host cellular reorganization in viral infection. These findings may enable us to understand the conserved pathways affected in eukaryotic cells as a result of viral protein expression. BACKGROUND The online version contains supplementary material available at 10.1007/s13205-020-02624-4.