GO annotations are created 2-Ethoxybenzamide manually, by expert curators, as well as by automatic systems such as HAMAP. In addition, annotation projects can also involve students such as the Community Annotation with Ontologies. The manual curation of GO terms is a central part of the workflow at UniProt, and UniProt is an active member of the GO consortium. Many UniProtKB keywords are also mapped to ONO-4059 equivalent GO terms, and the occurrence of a KW annotation allows the annotation of the equivalent GO term. This publication describes a project initiated by the SwissProt virus annotation team to study the complex interactions of viruses and their hosts and to encode this knowledge in a set of UniProt keywords, GO terms, and interlinked ViralZone pages. All organisms display an impressive battery of innate and acquired antiviral defenses. The viruses we observe today are ��escape artists�� with a talent for evading these defenses, and whose ability to manipulate their host is essential for virus survival. Their genomes are generally extremely small, encoding few proteins, and these need to be very efficient �C they often attack several key points of the host biology. For example, the Hepatitis B virus encodes only four proteins; the polymerase, capsid and surface proteins are essential for the basic life cycle of the virus while the HBX protein plays a major role in host immune defense evasion and cell transformation. Because of the limited coding capacity of most viral genomes, these entities have evolved surgical strikes to cut off multiple essential host defense pathways. An extensive study of the recent literature was performed to identify essential and conserved host-virus interactions. The number of interactions to consider is significant: as an example, the 13 proteins of HIV-1 have been shown to interact with more than 2589 human proteins, although not all such interactions may be physiologically relevant. We have focused on interactions that have been described for at least two different viruses, and confirmed by several independent laboratories.