Severe Acute Respiratory Syndrome Coronavirus Induces Differential Host Gene Expression Responses Associated with Pathogenesis

ABSTRACT

Abstract The newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV) exhibits unique characteristics with respect to its molecular biology, replication, transcription and assembly. Several cell types including Vero E6 cells are permissive for SARS-CoV replication with resultant cytopathic effects. Microarray analyses have elucidated the cellular expression patterns of human genes in response to SARS-CoV infection. These studies have revealed alterations in the transcription and translation of genes belonging to various functional groups including cell cycle, apoptosis, signal transduction, transcriptional regulation, host translation, protein modulators, protein trafficking, cytoskeletal network, cellular metabolism, and antiviral resistance. There is significant induction of heat shock proteins that are crucial to the immune response mechanism. Specific immune-related genes are upregulated, coinciding with the high cytokine profiles in SARS patients which incite proinflammatory responses. Modified levels of transcripts mediating proinflammatory and anti-inflammatory processes illustrate the balance between opposing forces during SARS pathogenesis. Another interesting phenomenon is the differential expression of genes that support both anti-apoptotic and proapoptotic processes. Thus, anti-apoptotic mechanisms facilitate the initial viral multiplication, whereas at later infection phase, apoptosis results in cell lysis to release viral progeny. Transcriptomic and proteomic analyses provide new insights into the host-pathogen interactions and pathophysiology of SARS-CoV infection. These critical interactions involve an elaborate interplay between various mechanisms to favor virus propagation before frank apoptosis and the triggering of specific pathways in host cells that attempt to eliminate the pathogen.