SERPING1 mRNA overexpression in monocytes from HIV+ patients

Inflamm Res. 2017 Dec;66(12):1107-1116. doi: 10.1007/s00011-017-1091-x. Epub 2017 Sep 9.

Abstract

Objective: The HIV-1 virus activates the complement system, an essential element of the immune system. SERPING1 is a protease inhibitor that disables C1r/C1s in the C1 complex of the classical complement pathway.

Methods: In this paper, we performed an analysis of several microarrays deposited in GEO dataset to demonstrate that SERPING1 mRNA is modulated in CD14+ monocytes from HIV-1-infected individuals. In addition, data were validated on monocytes isolated from seronegative healthy volunteers, treated with IFNs.

Results: Our analysis shows that SERPING1 mRNA is overexpressed in monocytes from HIV-1+ patients and the expression levels correlate positively with viral load and negatively with the CD4+ T-cell count. Of note, anti-retroviral therapy is able to reduce the levels of SERPING1 mRNA, ex vivo. In addition, we found that 30% of the SERPING1 genes network is upregulated in monocytes from HIV-1+ patients. Noteworthy, the expression levels of IFITM1-an antiviral molecule belonging to the genes network-correlate positively with SERPING1 expression. Interestingly, the monocytes treatment with IFN-gamma, IFN-beta and IFN-alpha significantly upregulates the SERPING1 mRNA expression levels.

Conclusions: From the outcome of our investigation, it is possible to conclude that SERPING1 and its network serve as important components of the innate immune system to restrict HIV-1 infection.

Keywords: C1-INH; Complement; HIV-1; IFN-gamma; Monocyte; SERPING1.

MeSH terms

  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes
  • Complement C1 Inhibitor Protein / genetics*
  • HIV Infections / genetics*
  • HIV Infections / virology
  • HIV-1
  • Humans
  • Monocytes / metabolism*
  • RNA, Messenger / metabolism*
  • Viral Load

Substances

  • Complement C1 Inhibitor Protein
  • RNA, Messenger
  • SERPING1 protein, human