Use of Functional Genomics to Understand Influenza–Host Interactions

Abstract

Infection with influenza typically results in mild-to-moderate illness in healthy individuals; however, it is responsible for 30,000-40,000 deaths each year in the United States. In extreme cases, such as the influenza pandemic of 1918, tens of millions of people have died from the infection. To prepare for future influenza outbreaks, it is necessary to understand how the virus interacts with the host and to determine what makes certain strains of influenza highly pathogenic. Functional genomics provides a unique approach to this effort by allowing researchers to examine the effect of influenza infection on global host mRNA levels. Researchers are making increasing use of this approach to study virus-host interactions using a variety of model systems. For example, data obtained using microarray technology, in combination with mouse and macaque infection models, is providing exciting new insights into the pathogenicity of the 1918 virus. These studies suggest that the lethality associated with this virus is in part due to an aberrant and unchecked immune response. Progress is also being made toward using functional genomics in the diagnosis and prognosis of acute lung infections and in the development of more effective influenza vaccines and antivirals.

Macaque Proteome Response to Highly Pathogenic Avian Influenza and 1918 Reassortant Influenza Virus Infections

“…These viral-host interactions are commonly species specific and do provide a formidable barrier to interspecies viral spread (36,40). While rodent model systems have been developed to study influenza virus infection (8), genetic and physiological differences compared to humans argue for a more physiologically relevant model (9). In light of this, several macaque species, including Macaca mulatta, Macaca nemestrina, and Macaca fascicularis, currently serve as physiologically relevant model systems for studying pathogenesis induced by human viruses, encompassing agents such as HIV, Ebola, variola major, and influenza A viruses (1,12).…”

Proteome Alterations in Primary Human Alveolar Macrophages in Response to Influenza A Virus Infection

“…The monocyte-derived macrophages produced in vitro may respond differently to viral infections than the natural macrophages that have differentiated in vivo . In addition, several previous studies on determining the global responses of hosts to influenza infections mainly focused on using DNA microarrays to analyze gene expression changes at the mRNA level 3, 5, 6 . The actual effector molecules in cells are proteins, and the abundances of mRNAs usually do not reflect the levels of corresponding proteins 7–9 .…”

Quantitative analysis of cellular proteome alterations in human influenza A virus‐infected mammalian cell lines

“…In addition, infections induce complex signal transduction pathways related to antiviral response of the host cells 3. Both events have an impact on host cell gene expression patterns 4 and therefore cause alterations in morphology and metabolic state of the cells and induce apoptosis. Whether apoptosis results from the inhibition of host cell gene expression, or is related to the antiviral response of the host cell, or by the virus itself is not completely understood.…”