ABSTRACT
Mechanisms of Virus-Induced Asthma 91
cause results from both the direct effects of the replicating virus on the cell and the response of the host to this infection. This response has both an innate component, which is fully functional before the viral organisms enter the cell, and an adaptive component, which has memory, specificity, and diversity. The virus first interacts with a cell by binding to specific receptors located on the cell membrane. Unfortunately, the receptors for many of the common respiratory viruses are either unknown or poorly characterized. Exceptions to this include the major group rhinoviruses, which bind to intercellular adhesion molecule-! (ICAM-1) (6) and the influenza virus, which binds to residues rich in sialic acid. After binding to specific cell surface receptors, viruses penetrate the cell membrane and become uncoated, such that free viral nucleic acid enters the cytoplasm (for most RNA viruses) or nucleus (for most DNA viruses) and undergo transcription into mRNA by viral polymerase enzymes and translation into viral proteins. For many singlestranded RNA viruses, the kinetics of viral replication involve production of complementary mRNA of opposite polarity of the entire viral genome, which can then be used as a template to make new full-length, viral genomic RNA (7). Transcription of individual mRNA species allows for translation into new viral proteins, and the newly synthesized viral genome and proteins assemble into complete particles called virions. The virions can then be released by budding from the cell surface or lysis of the cell to propagate the infection. For RSV, the control over whether the viral polymerase transcribes the entire genome or individual mRNAs for protein synthesis is tightly regulated by the cytoplasmic concentration of the viral nucleocapsid protein, such that a comparatively high concentration of this protein favors the transcription of full-length mRNA, and vice versa. For adenoviruses, a double-stranded DNA virus, the kinetics of viral replication involve the expression of "early"genes, which use host cell mechanisms to synthesize viral mRNA and proteins that are important to the subsequent replication of viral DNA. The "late" genes are responsible for producing structural proteins, which are transported from the cytoplasm to the nucleus for assembly of virions and the complete virus returns to the cytoplasm to be shed or released by cell lysis.
