Quantitative proteomics analysis reveals unique but overlapping protein signatures in HIV infections

Al-Mozaini, Maha; Alzahrani, Alhusain J.; Alsharif, Ibtihaj; Shinwari, Zakia; Halim, Magid; Alhokail, Abdullah; Alrajhi, Abdulrahman A.; Alaiya, Ayodele

doi:10.1016/j.jiph.2021.03.009

Cited by 5 publications

(2 citation statements)

References 35 publications

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“…Mass spectrometry-based proteomics of human serum and plasma has been used for identifying markers for disease diagnosis [14], and for the study of viral infections such as influenza [15], COVID-19 [16,17], and HIV [18]. Characterizing the host response to CMV infection will allow for an increased understanding biological events associated with CMV infection severity and will also provide insights into the negative impact of CMV infection on the transplanted organ.…”

Section: Introductionmentioning

confidence: 99%

Plasma proteome perturbation for CMV DNAemia in kidney transplantation

Sigdel¹,

Boada²,

Kerwin³

et al. 2023

PLoS ONE

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Background Cytomegalovirus (CMV) infection, either de novo or as reactivation after allotransplantation and chronic immunosuppression, is recognized to cause detrimental alloimmune effects, inclusive of higher susceptibility to graft rejection and substantive impact on chronic graft injury and reduced transplant survival. To obtain further insights into the evolution and pathogenesis of CMV infection in an immunocompromised host we evaluated changes in the circulating host proteome serially, before and after transplantation, and during and after CMV DNA replication (DNAemia), as measured by quantitative polymerase chain reaction (QPCR). Methods LC-MS-based proteomics was conducted on 168 serially banked plasma samples, from 62 propensity score-matched kidney transplant recipients. Patients were stratified by CMV replication status into 31 with CMV DNAemia and 31 without CMV DNAemia. Patients had blood samples drawn at protocol times of 3- and 12-months post-transplant. Additionally, blood samples were also drawn before and 1 week and 1 month after detection of CMV DNAemia. Plasma proteins were analyzed using an LCMS 8060 triple quadrupole mass spectrometer. Further, public transcriptomic data on time matched PBMCs samples from the same patients was utilized to evaluate integrative pathways. Data analysis was conducted using R and Limma. Results Samples were segregated based on their proteomic profiles with respect to their CMV Dnaemia status. A subset of 17 plasma proteins was observed to predict the onset of CMV at 3 months post-transplant enriching platelet degranulation (FDR, 4.83E-06), acute inflammatory response (FDR, 0.0018), blood coagulation (FDR, 0.0018) pathways. An increase in many immune complex proteins were observed at CMV infection. Prior to DNAemia the plasma proteome showed changes in the anti-inflammatory adipokine vaspin (SERPINA12), copper binding protein ceruloplasmin (CP), complement activation (FDR = 0.03), and proteins enriched in the humoral (FDR = 0.01) and innate immune responses (FDR = 0.01). Conclusion Plasma proteomic and transcriptional perturbations impacting humoral and innate immune pathways are observed during CMV infection and provide biomarkers for CMV disease prediction and resolution. Further studies to understand the clinical impact of these pathways can help in the formulation of different types and duration of anti-viral therapies for the management of CMV infection in the immunocompromised host.

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Section: Introductionmentioning

confidence: 99%

Plasma proteome perturbation for CMV DNAemia in kidney transplantation

Sigdel¹,

Boada²,

Kerwin³

et al. 2023

PLoS ONE

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show abstract

“…Evaluation of peripheral mRNA changes from clinical and sub-clinical CMV primary infection and reactivation has provided insight into causal factors for allograft dysfunction secondary to CMV [4][5][6] , host biological pathways actively altered by the virus 7 , and the dynamic temporal changes of cell cycle, DNA damage molecules [8][9][10][11][12] that occur during the evolution of CMV viral replication 13 . Mass spectrometry-based proteomics of human serum and plasma has been used for identifying markers for disease diagnosis 14 , and for the study of viral infections such as influenza 15 , COVID-19 16,17 , and HIV 18 . Characterizing the host response to CMV infection will allow for an increased understanding biological events associated with CMV infection severity and will also provide insights into the negative impact of CMV infection on the transplanted organ.…”

Section: Introductionmentioning

confidence: 99%

Plasma Proteome Perturbation for CMV DNAemia in Kidney Transplantation

Sigdel

Boada

Kerwin

et al. 2022

Preprint

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Background. Cytomegalovirus (CMV) infection, either de novo or as reactivation after allotransplantation and chronic immunosuppression, is recognized to cause detrimental alloimmune effects, inclusive of higher susceptibility to graft rejection and substantive impact on chronic graft injury and reduced transplant survival. To obtain further insights into the evolution and pathogenesis of CMV infection in an immunocompromised host we evaluated changes in the circulating host proteome serially, before and after transplantation, and during and after CMV DNA replication (DNAemia), as measured by quantitative polymerase chain reaction (QPCR). Methods. LC-MS-based proteomics was conducted on 168 serially banked plasma samples, from 62 propensity score-matched kidney transplant recipients. Patients were stratified by CMV replication status into 31 with CMV DNAemia and 31 without CMV DNAemia. Patients had blood samples drawn at protocol times of 3- and 12-months post-transplant. Additionally, blood samples were also drawn before and 1 week and 1 month after detection of CMV DNAemia. Plasma proteins were analyzed using an LCMS 8060 triple quadrupole mass spectrometer. Further, public transcriptomic data on time matched PBMCs samples from the same patients was utilized to evaluate integrative pathways. Data analysis was conducted using R and Limma. Results. Samples were segregated based on their proteomic profiles with respect to their CMV Dnaemia status. A subset of 17 plasma proteins was observed to predict the onset of CMV at 3 months post-transplant enriching platelet degranulation (FDR, 4.83E-06), acute inflammatory response (FDR, 0.0018), blood coagulation (FDR, 0.0018) pathways. An increase in many immune complex proteins were observed at CMV infection. Prior to DNAemia the plasma proteome showed changes in the anti-inflammatory adipokine vaspin (SERPINA12), copper binding protein ceruloplasmin (CP), complement activation (FDR=0.03), and proteins enriched in the humoral (FDR=0.01) and innate immune responses (FDR=0.01). Conclusion. Plasma proteomic and transcriptional perturbations impacting humoral and innate immune pathways are observed during CMV infection and provide biomarkers for CMV disease prediction and resolution. Further studies to understand the clinical impact of these pathways can help in the formulation of different types and duration of anti-viral therapies for management of CMV infection in the immunocompromised host.

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