Molecular Characteristics of Organic Matters in PM2.5 Associated with Upregulation of Respiratory Virus Infection in Vitro

The extent to which organic matters (OM) in PM_2.5 affect virus infections and the key organic molecules involved in this process remain unclear. Herein, this study utilized ultra-high resolution mass spectrometry coupled with in vitro experiments to identify the organic molecules associated with respiratory virus infection for the first time. Water-soluble organic matters (WSOM) and water-insoluble organic matters (WIOM) were separated from PM_2.5 samples collected at the urban area of Guangzhou, China. Their molecular compositions were analyzed using Fourier transform ion cyclotron resonance mass spectrometry. Subsequently, in vitro experiments were conducted to explore the impact of WSOM and WIOM exposure on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudo-virus infection in A549 cells. Results revealed that WSOM and WIOM respectively promoted 1.7 to 2.1-fold and 1.9 to 3.5-fold upregulation of SARS-CoV-2 pseudo-virus infection in a concentration-dependent manner (at 25 to 100 μg mL^-1) compared to the virus-only control group. Partial least squares model analysis indicated that the increased virus infection was likely related to phthalate ester and nitro-aromatic molecules in WSOM, as well as Lipid_C molecules with aliphatic and olefinic structures in WIOM. Interestingly, the molecules responsible for upregulating SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) expression and virus infection differed. Thus, it was concluded that ACE2 upregulation alone may not fully elucidate the mechanisms underlying increased susceptibility to virus infection. The findings highlight the critical importance of aromatic and lipid molecules found in OM in relation to respiratory virus infection.