Abstract
Human immunodeficiency virus (HIV)-infected long-term non-progressors (LTNPs) are of particular importance because of their unique disease progression characteristics. Defined by the maintenance of normal CD4+T cells after more than 8 years of infection, these LTNPs are heterogeneous. Some LTNPs exhibit ongoing viral production, while others do not and are able to control viral production. The underlying basis for this heterogeneity has not been clearly elucidated. In this study, the miRNA expression profiles of LTNPs were assessed. The levels of microRNA-19b (miR-19b) were found to be significantly increased in peripheral blood mononuclear cells of LTNPs with lower rather than higher viral load. We made clear that miR-19b may regulate CD8+T cell functions in HIV infection, which has not been addressed before. Overexpression of miR-19b promoted CD8+T cell proliferation, as well as interferon-γ and granzyme B expression, while inhibiting CD8+T cells apoptosis induced by anti-CD3/CD28 stimulation. The target of miR-19b was found to be the “phosphatase and tensin homolog”, which regulates CD8+T cells function during HIV infections. Furthermore, we found that miR-19b can directly inhibit viral production in in-vitro HIV infected T cells. These results highlight the importance of miR-19b to control viral levels, which facilitate an understanding of human immunodeficiency virus pathogenesis and provide potential targets for improved immune intervention.
Highlights
Human immunodeficiency virus (HIV) infected patients with atypical disease progression are of particular importance because they can provide important information regarding HIV pathogenesis and therapy
The nine long-term non-progressors (LTNPs) were divided into two groups, one of which was very close to the typical progressors (TPs) (Group A, n = 6) and another that was intertwined with the healthy controls (HCs) (Group B, n = 3) (Figure 1A)
By comparison of clinical characteristics, we found that viral load was the only significantly different parameter between the two groups of LTNPs (P = 0.024, Figure 1B)
Summary
Human immunodeficiency virus (HIV) infected patients with atypical disease progression are of particular importance because they can provide important information regarding HIV pathogenesis and therapy. The first evidence of long-term non-progressors (LTNPs) was reported in 1993, showing that 15% of individuals infected with HIV maintain a CD4 count >500 cells/μl [1, 2]. MiR-19b Regulates PTEN in LTNPs. In 2005, study showed that ∼1/300 HIV-infected patients had undetectable plasma HIV RNA loads without antiretroviral therapy (ART) [3]. ECs with lower CD4+ T cell numbers were similar to ART-treated patients, but different from HIV-1-negative individuals [12]. LTNPs maintaining high viral loads are prone to long-term disease progression, with reduced life expectancy compared to HIV negative individuals [14, 15]. Analysis of the underlying reason for the differing levels of viral control in LTNPs may facilitate an understanding of HIV pathogenesis and may provide for new approaches to immune intervention
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