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Modulation of gene expression in CD4+ T lymphocytes following in vitro HIV infection: a comparison between human and chimpanzee.

ABSTRACT: Chimpanzees are susceptible to experimental infection by human deficiency virus (HIV)-1, but unlike humans, they exceptionally develop an immunodeficiency syndrome after HIV-1 inoculation. To explore the difference between human and chimpanzee, we analyzed the expression of 1547 genes of various functions in human or chimpanzee CD4+ lymphoblasts inoculated in vitro with HIV-1. We observed that, 1 day after HIV inoculation, fifty-eight genes were up-regulated in lymphoblasts of the three humans while their expression remained unchanged in lymphoblasts of the three chimpanzees. One gene is involved in adhesion of HIV (catenin-alpha), three in the immune response (semaphorin 4D, placental growth factor, IL-6), three in apoptosis (deleted in colorectal carcinoma, caspase 9 and FOXO1A). No difference between species was revealed for the expression of 373 genes related to glycosylation pathways. The in vitro human/chimpanzee comparison reveals new candidate genes up-regulated after inoculation with HIV-1 only in human lymphoblasts and which could be related to the higher sensitivity of human to HIV-induced AIDS.

SUBMITTER: Puissant-Lubrano B

PROVIDER: S-EPMC4585051 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Modulation of gene expression in CD4+ T lymphocytes following in vitro HIV infection: a comparison between human and chimpanzee.

Puissant-Lubrano Bénédicte B Apoil Pol-André PA Gleizes Arnaud A Forestier Lionel L Julien Raymond R Winterton Peter P Pasquier Christophe C Izopet Jacques J Blancher Antoine A

Virusdisease 20150606 1-2

Chimpanzees are susceptible to experimental infection by human deficiency virus (HIV)-1, but unlike humans, they exceptionally develop an immunodeficiency syndrome after HIV-1 inoculation. To explore the difference between human and chimpanzee, we analyzed the expression of 1547 genes of various functions in human or chimpanzee CD4+ lymphoblasts inoculated in vitro with HIV-1. We observed that, 1 day after HIV inoculation, fifty-eight genes were up-regulated in lymphoblasts of the three humans w ...[more]

PMID: 26436123

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Project description:Assessment of the extent to which the altered profiles of miRNA expression influence viral replication and latency, as well as the efficiency of host defenses, may be useful for understanding the basis of the HIV-1-related alterations in cellular physiology and immunologic control. To this end, three patient groups were enrolled. One group consisted of subjects who were classified as M-CM-)lite control long-term non-progressors (M-CM-)LTNP). A second study group was HIV-1-positive subjects, who were antiretroviral therapy naive. A third group was multiply exposed to HIV-1, but uninfected (MEU). This study allowed us to investigate the existence of a CD4+T- lymphocytes miRNAs signature able to discriminate among different stages of HIV-1 infection, and to evaluate whether the exposure to HIV-1 antigen is sufficient to change the miRNA profile. MicroRNAs inhibit HIV-1 expression by either modulating host innate immunity or by directly interfering with viral mRNAs. We evaluated the expression of 377 miRNAs in CD4+ T cells from HIV-1 M-CM-)lite LTNP (M-CM-)LTNP), naive and multiply exposed uninfected individuals (MEU) and we observed that the M-CM-)LTNP patients clustered with naive, whereas all MEU subjects grouped together. The discriminatory power of miRNAs showed that 21 miRNAs significantly differentiated M-CM-)LTNP from MEU and 23 miRNAs distinguished naive from MEU, while only 1 (miR-155) discriminated M-CM-)LTNP from naive. We proposed that miRNA expression may discriminate between HIV-1 infected and exposed but negative individuals. Analysis of miRNAs expression after exposure of healthy CD4+T cells to gp120 in vitro confirmed our hypothesis that a miRNA profile could be the result not only of a productive infection, but also of the exposure to HIV-1 products that leave a signature in immune cells. The comparison of normalized Dicer and Drosha expression in ex vivo and in vitro conditions revealed that these enzymes did not affect the change of miRNA profiles, supporting the existence of a Dicer-independent biogenesis pathway. We have compared miRNA profiles of CD4+ T-lymphocytes from 18 HIV-1-exposed subjects with healthy CD4+ T-lymphocytes following exposure to gp120 using a RT-qPCR assay.

Project description:Assessment of the extent to which the altered profiles of miRNA expression influence viral replication and latency, as well as the efficiency of host defenses, may be useful for understanding the basis of the HIV-1-related alterations in cellular physiology and immunologic control. To this end, three patient groups were enrolled. One group consisted of subjects who were classified as élite control long-term non-progressors (éLTNP). A second study group was HIV-1-positive subjects, who were antiretroviral therapy naive. A third group was multiply exposed to HIV-1, but uninfected (MEU). This study allowed us to investigate the existence of a CD4+T- lymphocytes miRNAs signature able to discriminate among different stages of HIV-1 infection, and to evaluate whether the exposure to HIV-1 antigen is sufficient to change the miRNA profile. MicroRNAs inhibit HIV-1 expression by either modulating host innate immunity or by directly interfering with viral mRNAs. We evaluated the expression of 377 miRNAs in CD4+ T cells from HIV-1 élite LTNP (éLTNP), naive and multiply exposed uninfected individuals (MEU) and we observed that the éLTNP patients clustered with naive, whereas all MEU subjects grouped together. The discriminatory power of miRNAs showed that 21 miRNAs significantly differentiated éLTNP from MEU and 23 miRNAs distinguished naive from MEU, while only 1 (miR-155) discriminated éLTNP from naive. We proposed that miRNA expression may discriminate between HIV-1 infected and exposed but negative individuals. Analysis of miRNAs expression after exposure of healthy CD4+T cells to gp120 in vitro confirmed our hypothesis that a miRNA profile could be the result not only of a productive infection, but also of the exposure to HIV-1 products that leave a signature in immune cells. The comparison of normalized Dicer and Drosha expression in ex vivo and in vitro conditions revealed that these enzymes did not affect the change of miRNA profiles, supporting the existence of a Dicer-independent biogenesis pathway.

Dataset Information

Modulation of gene expression in CD4+ T lymphocytes following in vitro HIV infection: a comparison between human and chimpanzee.

Publications

Modulation of gene expression in CD4+ T lymphocytes following in vitro HIV infection: a comparison between human and chimpanzee.

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