Quantitative Proteomics by SWATH-MS Reveals Altered Expression of Nucleic Acid Binding and Regulatory Proteins in HIV-1-Infected Macrophages

Human
immunodeficiency virus type 1 (HIV-1) infection remains a worldwide
epidemic, and innovative therapies to combat the virus are needed.
Developing a host-oriented antiviral strategy capable of targeting
the biomolecules that are directly or indirectly required for viral
replication may provide advantages over traditional virus-centric
approaches. We used quantitative proteomics by SWATH-MS in conjunction
with bioinformatic analyses to identify host proteins, with an emphasis
on nucleic acid binding and regulatory proteins, which could serve
as candidates in the development of host-oriented antiretroviral strategies.
Using SWATH-MS, we identified and quantified the expression of 3608
proteins in uninfected and HIV-1-infected monocyte-derived macrophages.
Of these 3608 proteins, 420 were significantly altered upon HIV-1
infection. Bioinformatic analyses revealed functional enrichment for
RNA binding and processing as well as transcription regulation. Our
findings highlight a novel subset of proteins and processes that are
involved in the host response to HIV-1 infection. In addition, we
provide an original and transparent methodology for the analysis of
label-free quantitative proteomics data generated by SWATH-MS that
can be readily adapted to other biological systems.