The invention provides for a full-length cloned cDNA copy of the RNA genome of a predominant norovirus strain (Genogroup II.4) designated MD145-12 that was associated with human gastrointestinal illness. The noroviruses, which were formerly known as "Norwalk-like" viruses are estimated to cause 23 million cases of acute gastroenteritis in the USA each year. The virus has been designated into category B of the CDC biodefense-related priority pathogens because it can be used as an agent of bioterrorism. The subject cDNA clone of the virus encodes proteins of the MD145-12 strain that, when expressed in vitro, exhibit properties that would be expected from those produced by the original infectious virus. This cDNA clone is presently the only source to obtain norovirus proteins to facilitate studies aimed at developing control strategies such as vaccines and therapeutic drugs.