Cellular Scent of Influenza Virus Infection.

Abstract

Volatile organic compounds (VOCs) emanating from humans have the potential to revolutionize non-invasive diagnostics. Yet, little is known about how these compounds are generated by complex biological systems, and even less is known about how these compounds are reflective of a particular physiological state. In this proof-of-concept study, we examined VOCs produced directly at the cellular level from B lymphoblastoid cells upon infection with three live influenza virus subtypes: H9N2 (avian), H6N2 (avian), and H1N1 (human). Using a single cell line helped to alleviate some of the complexity and variability when studying VOC production by an entire organism, and it allowed us to discern marked differences in VOC production upon infection of the cells. The patterns of VOCs produced in response to infection were unique for each virus subtype, while several other non-specific VOCs were produced after infections with all three strains. Also, there was a specific time course of VOC release post infection. Among emitted VOCs, production of esters and other oxygenated compounds was particularly notable, and these may be attributed to increased oxidative stress resulting from infection. Elucidating VOC signatures that result from the host cells response to infection may yield an avenue for non-invasive diagnostics and therapy of influenza and other viral infections.

Volatile emanations fromin vitroairway cells infected with human rhinovirus

“…Other compounds observed in this study, specifically oxidative stress products, may also be informative. For example, the distribution of produced VOCs in this study is different from that for the influenza infection (Aksenov et al, 2014, in press), which may bear phenomenologic significance (Wood et al, 2006). Future studies are needed to correlate the distributions of oxidative stress products with the underlying cause.…”

“…Dimethyl sulfide is likely a cleavage product of cysteine and methionine amino acids residues (del Castillo-Lozano et al, 2008) which contribute to volatile emissions during proteolysis. A similar sulfur compound, thiirane, was found to be produced by B cells when infected with influenza A virus (Aksenov et al, 2014, in press). The identification of dimethyl sulfide in our study suggests that viruses (HRV, and possibly influenza) cause protein cleavage as do bacteria.…”

“…Even though some of the compounds are not identified unambiguously, it is clear that the majority of the detected compounds are long chain/branched aliphatic compounds, predominantly alkanes/alkenes and alcohols. These compounds—specifically alkanes and methylated alkanes—were previously reported as biomarkers of live attenuated influenza viral vaccination in breath (Phillips et al, 2003a, Phillips et al, 2003b, Phillips et al, 2000, Phillips et al, 2010) and they are also produced in a single cell culture (B cells) when infected with influenza A virus (Aksenov et al, 2014, in press). The production of these compounds is linked to oxidative stress during the infection (Schwarz, 1996) due to peroxidative cleavage of lipids (Phillips et al, 2000).…”

“…Aksenov et al described VOC profile changes of human B-cell leukocytes after infection with multiple influenza virus strains and found production of VOCs associated with oxidative stress (Aksenov et al, 2014, in press). Earlier clinical studies found a subset of these VOCs in exhaled breath of patients treated with live attenuated influenza vaccine (Phillips et al, 2010), although the detailed mechanisms by which these VOCs are produced remains unclear.…”

A Compendium of Volatile Organic Compounds (VOCs) Released By Human Cell Lines

“…Cell culture studies should be also useful in identifying compounds, which are associated with a specific phenotype, e.g . oncogenic transformation [53, 57-69], or infection [63, 70]. Moreover, primary cells from humans and genetically altered animals may be analyzed to establish genotype/phenotype relationships for particular VOCs.…”