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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. [ABSTRACT FROM AUTHOR]

The natural history of HIV infection has been greatly changed by the introduction of highly active antiretroviral therapy (HAART). As a consequence of improved immune function, the incidence of AIDS-defining cancers (ADCs), such as Kaposi's sarcoma, non- Hodgkin's lymphoma (NHL) and invasive cervical cancer, has significantly declined. On the contrary, non-AIDS-defining cancers (NADCs), such as hepatocellular carcinoma, anal cancer, lung cancer, colorectal cancer and Hodgkin's lymphoma, have gradually emerged as a major fraction of the overall cancer burden. The reasons are still partially unknown. Some of the increased risk may be explained by a high prevalence of cancer risk factors, such as smoking, alcohol consumption, human papilloma virus (HPV) infection and HCV infection among HIV-infected people. The role of immunosuppression in the development of NADCs is controversial, as several studies have not found a clear-cut evidence of an association between the degree of immunosuppression and the development of NADCs. Analogously, the impact of HAART is still not well defined. Future research should focus on the etiology of NADCs, in order to shed light on the pathogenesis of cancer and ultimately to work for prevention; moreover, additional studies should evaluate the best therapeutic approaches to NADCs and the impact of cancer screening interventions among HIV-infected people, in an effort to diagnose cancer at an earlier stage. [ABSTRACT FROM AUTHOR]

Objectives Human Immunodeficiency Virus (HIV) infection can induce neurocognitive complications classified as HIV-associated neurocognitive disorder (HAND). The chitinase family is associated with innate immunity cells and many infectious diseases. Methods We analyzed microarray datasets obtained from NCBI in order to verify the expression of chitinase family genes in hippocampus of uninfected rhesus macaques versus those with histopathologic evidence of Simian Immunodeficiency Virus Encephalitis (SIVE). Moreover, we have analysed two human microarray datasets to verify the results obtained in macaques hippocampus affected by SIVE. For these studies, we have also used the open source tools Genome-scale Integrated Analysis of gene Networks in Tissues (GIANT) to identify the chitinase genes network. Results CHIT1, CHI3L1 and CHI3L2 levels were significantly increased in SIVE hippocampus as compared to non-infected control specimens. Furthermore, we found a negative correlation between CHIA vs. Brain Viral Load (BVL). These data was confirmed partially in human brain section of HAD/HIVE subjects. Also, we showed that HIV-1 was able to modulate the expression of CHIT1, CHI3L1, CHI3L2 and CHID1 in human macrophages. Conclusions These results suggest that chitinase gene expression is altered in SIVE and in HAD/HIVE brain sections and call for more studies examining whether this is a protective immunological reaction or a destructive tissue response to encephalitis. [ABSTRACT FROM AUTHOR]

Objectives T-cell repertoire dysfunction characterizes human immunodeficiency virus type 1 (HIV-1) infection, but the pathogenic mechanisms remain unclear. Disease progression is probably due to a profound dysregulation of Th1, Th2, Th17 and Treg patterns. The aim of this study was to analyze the features of CD4+ T cells in HIV-positive patients with different viroimmunological profile. Methods we used a gene expression dataset of CD4+ T cells from healthy donors, HIV+ naive patients and Elite Controllers (EC), obtained from the NCBI Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/ , accession number GSE18233). Results Principal Component Analysis (PCA) showed an almost complete overlap between the HIV-infected and EC patients, which cannot easily explain the different responses to HIV infection of these two group of patients. We have found that HIV patients and the EC showed an upregulation of the Th1 pro-inflammatory cytokines and chemokines, compared to the controls. Also, we have surprisingly identified IL28B, which resulted downregulated in HIV and EC compared to healthy controls. We focused attention also on genes involved in the constitution of the immunological synapse and we showed that HLA class I and II genes resulted significantly upregulated in HIV and in EC compared to the control. In addition to it, we have found the upregulation of others syncytial molecules, including LAG3, CTLA4, CD28 and CD3, assisting the formation of syncytia with APC cells. Conclusions Understanding the mechanisms of HIV-associated immunological chaos is critical to strategically plan focused interventions. [ABSTRACT FROM AUTHOR]