Other than the few genome-encoded enzymes, viruses must depend on their host’s machinery for nearly all aspects of their life-cycle. Therefore it is not surprising that viruses use short functional motifs for binding to host proteins and recruiting host proteins to posttranslationally modify and traffic viral proteins to specific subcellular compartments. Although some reviews have summarized how a specific motif is used by viruses, the broad-based exploitation of short motifs by viruses has not been previously summarized (7
shows a collection of motifs that are commonly used by viruses to acquire host molecular machinery. In general, many types of viruses use these motifs at all stages of their life-cycles, and utilization of these motifs is not limited to specific species, with motifs used by many different species of plants and animals. Viruses exploit the ability of host enzymes to posttranslationally modify their proteins. In addition to the sources in , several previous reviews cover the myristoylation, prenylation, N-glycosylation, phosphorylation, and cleavage of viral proteins by host enzymes (9
Viruses also take advantage of a number of known short binding motifs for binding to host proteins. In addition to the sources presented in , previous reviews cover the viral use of motifs to bind host SH2 domains, PDZ domains, retinoblastoma protein (Rb), and Integrin receptors (21
). Many viral proteins are known to have immunoreceptor tyrosine based motifs (ITAMs) that are usually found in transmembrane immune receptors.
Quite often viral consensus binding or posttranslational modification motifs are critical for the viral life-cycle and viral replication. A few of the many examples are provided. A PxxP motif in HIV Nef activates Src family kinases and is important for HIV replication (28
). A PPPY motif in Marbug Virus VP40 protein is important for its interaction with Tsg101 and viral budding (30
). The N-myristoylation motif on the East African Cassava Mosaic Cameroon virus AC4 protein is responsible for plasma membrane targeting and pathogenicity (31
). The carboxy-terminal PDZ binding motif of the E6 human papillomavirus protein is important for viral proliferation and maintenance of viral copy number (32
There are many motifs in viral proteins that are important for the viral life-cycle but for which host targets are not yet known or perhaps mediate interaction between two viral proteins. For example, a YPPL motif in F13L vaccinia virus protein is required for efficient release of extracellular enveloped viruses (33
). A KKR motif in cytoplasmic tail of Nef in Nipah Virus is important for its fusogenic activity (34
). A PGQM motif in Gag is required for HIV infection (35
). A WxxF motif found in Vif mediates interaction with Vpr (37
So why are short functional motifs so critical for viral function? One possibility is that viruses select motifs because motifs are often involved in the regulation of host molecules; the virus needs to deregulate pathways and then re-regulate these pathways to suit its needs. Therefore, motifs provide ready access to switching on and off specific cell processes, effectively allowing reprogramming of the cell. A single consensus motif may also provide the virus access to many factors that bind this motif. For example, a viral PxxP motif may target an array of different host factors containing SH3 domains. Short motifs may also provide a means by which the virus uses its small proteome to acquire many different host functions.