Preferential upregulation of interferon-alpha subtype 2 expression in HIV-1 patients.
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Preferential upregulation of interferon-alpha subtype 2 expression in HIV-1 patients. / Lehmann, C; Taubert, D; Jung, N; Fätkenheuer, G; van Lunzen, Jan; Hartmann, P; Romerio, F.
In: AIDS RES HUM RETROV, Vol. 25, No. 6, 6, 2009, p. 577-581.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Preferential upregulation of interferon-alpha subtype 2 expression in HIV-1 patients.
AU - Lehmann, C
AU - Taubert, D
AU - Jung, N
AU - Fätkenheuer, G
AU - van Lunzen, Jan
AU - Hartmann, P
AU - Romerio, F
PY - 2009
Y1 - 2009
N2 - Humans tailor virus-specific immune responses through modulated expression of 12 different interferon (IFN)-alpha subtypes. However, exacerbated expression of certain IFN-alpha subtypes causes immunopathology in the context of autoimmune conditions and chronic viral infections. We showed that progression to AIDS is associated with elevated expression of IFN-alpha in unstimulated peripheral blood mononuclear cells. Here, we sought to determine whether distinct IFN-alpha subtypes are involved in this phenomenon. We used quantitative RT-PCR to assess expression levels of 12 IFN-alpha subtypes in peripheral blood mononuclear cells from normal donors and HIV-1 patients at CDC stage A and stage C of the disease. Three patterns of IFN-alpha subtype expression emerged. First, IFN-alpha2 and IFN-alpha6 mRNA levels were elevated in both patient groups. Second, IFN-alpha1/13, IFN-alpha8, IFN-alpha14, IFN-alpha16, IFN-alpha17, and IFN-alpha21 were upregulated in stage C but not stage A patients. Third, expression levels of IFN-alpha4, IFN-alpha5, IFN-alpha7, and IFN-alpha10 did not change among the three groups of volunteers. Among all other subtypes, IFN-alpha2 was preferentially upregulated, showing >60-fold higher levels in stage A and >400-fold in stage C patients compared with controls, which correlated with declining CD4 counts. Our results demonstrate that distinct IFN-alpha subtypes are sequentially activated during HIV-1 infection, which may be predictive of disease progression.
AB - Humans tailor virus-specific immune responses through modulated expression of 12 different interferon (IFN)-alpha subtypes. However, exacerbated expression of certain IFN-alpha subtypes causes immunopathology in the context of autoimmune conditions and chronic viral infections. We showed that progression to AIDS is associated with elevated expression of IFN-alpha in unstimulated peripheral blood mononuclear cells. Here, we sought to determine whether distinct IFN-alpha subtypes are involved in this phenomenon. We used quantitative RT-PCR to assess expression levels of 12 IFN-alpha subtypes in peripheral blood mononuclear cells from normal donors and HIV-1 patients at CDC stage A and stage C of the disease. Three patterns of IFN-alpha subtype expression emerged. First, IFN-alpha2 and IFN-alpha6 mRNA levels were elevated in both patient groups. Second, IFN-alpha1/13, IFN-alpha8, IFN-alpha14, IFN-alpha16, IFN-alpha17, and IFN-alpha21 were upregulated in stage C but not stage A patients. Third, expression levels of IFN-alpha4, IFN-alpha5, IFN-alpha7, and IFN-alpha10 did not change among the three groups of volunteers. Among all other subtypes, IFN-alpha2 was preferentially upregulated, showing >60-fold higher levels in stage A and >400-fold in stage C patients compared with controls, which correlated with declining CD4 counts. Our results demonstrate that distinct IFN-alpha subtypes are sequentially activated during HIV-1 infection, which may be predictive of disease progression.
KW - Adult
KW - Humans
KW - Male
KW - Female
KW - Middle Aged
KW - Cells, Cultured
KW - Up-Regulation
KW - Gene Expression Profiling methods
KW - HIV Infections immunology
KW - HIV-1 immunology
KW - Interferon-alpha biosynthesis
KW - Leukocytes, Mononuclear immunology
KW - Reverse Transcriptase Polymerase Chain Reaction methods
KW - Adult
KW - Humans
KW - Male
KW - Female
KW - Middle Aged
KW - Cells, Cultured
KW - Up-Regulation
KW - Gene Expression Profiling methods
KW - HIV Infections immunology
KW - HIV-1 immunology
KW - Interferon-alpha biosynthesis
KW - Leukocytes, Mononuclear immunology
KW - Reverse Transcriptase Polymerase Chain Reaction methods
M3 - SCORING: Zeitschriftenaufsatz
VL - 25
SP - 577
EP - 581
JO - AIDS RES HUM RETROV
JF - AIDS RES HUM RETROV
SN - 0889-2229
IS - 6
M1 - 6
ER -