Noninfectious papilloma virus–like particles inhibit HIV-1 replication: implications for immune control of HIV-1 infection by IL-27

Abstract

Human papilloma virus (HPV)- IntroductionIt has been demonstrated that both innate and adaptive immune response regulate HIV-1 replication, 1-10 and certain cell types secrete soluble HIV-1-suppressing proteins in response to various stimuli. [11][12][13][14][15] For example, secretion of anti-HIV ␤-chemokines and CD8 antiviral factor (CAF) from human T-lymphotropic virus (HTLV)-type 1 and herpes virus saimiri-infected cell line have been described. [11][12][13][14][15] Although a combination of antibodies and suppressive factors was able to reverse the inhibitory activity of CAF, complete reversal of HIV-1 suppression was not observed, suggesting that additional unknown suppressive factors were involved. 16 Certain microbial organisms elicit immune responses that reduce clinical HIV-1 infection presumably through the induction of soluble suppressive factors. Some persons who are simultaneously infected with HIV-1 and either dengue, Orienta tsutsugamushi, hepatitis G/GB virus C, or measles morbilli virus have reduced viral loads compared with patients who are infected with HIV-1 alone or with HIV-1 and other pathogens. [17][18][19][20][21][22][23][24][25] In the case of hepatitis G virus (HGV), the mechanism of action is postulated to be via binding of the serum HGV E2 protein to CD81, leading to increased regulated on activation normal T expressed and secreted protein (RANTES) secretion and reduced CCR5 expression. 24 In vitro studies have shown that HTLV-type 2 infection might up-regulate the production of macrophage inflammatory protein-1␣ . 26 Recent studies demonstrate that human papillopma virus-like particles (HPV-VLPs) bind to dendritic cells and are able to induce a range of responses in immune cells, notably the expression of anti-HIV-1 cytokines such as interferon-␣ (IFN-␣), interleukin-10 (IL-10), interferon-␥ (IFN-␥), and monocyte chemotactic protein 2 (MCP-2). 27,28 The HPV-VLP vaccine has been demonstrated to be protective against HPV infection. 29-31 HPV-type 16 (HPV16) represents the primary causative agent of cervical cancer. 32 The HPV16 VLPs, composed of the L1 major capsid protein, form nonenveloped icosahedral particles that lack viral DNA but both morphologically and immunologically resemble native virions. 33 Studies suggest that a potent immune response induced by VLPs is through the Toll-like receptor (TLR)/MyD88 pathway in dendritic cells. 27 In the current work, we evaluated the impact of VLPs on HIV-1 replication. Our results demonstrated that VLPs strongly inhibit replication of X4 and R5 HIV-1 in peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages (MDMs). It was discovered that the anti-HIV-1 activity of VLPs involved the release of suppressive factors. Gene expression profiles of PBMCs and MDMs demonstrated that VLP treatment up-regulated numerous potential antiviral genes along with the induction of recently described cytokine . Subsequent experiments demonstrated that recombinant IL-27 was able to inhibit X4 and R5 HIV replication. Taken together, these s...

M-CSF Inhibits Anti–HIV-1 Activity of IL-32, but They Enhance M2-like Phenotypes of Macrophages

“…2), an increased serum level of IL-32 might result in the acceleration of HIV-1 replication or spread in vivo. Recently, IL-27 has been shown to inhibit HIV-1 replication in macrophages (38,39). Interestingly, we found that M-CSF also significantly reduced the anti-HIV-1 activity of IL-27 (data not shown).…”

The role of BST‐2/Tetherin in host protection and disease manifestation

“…Treatment of monocytes and T cells with IL‐27 induces BST‐2 in an IFN signaling‐independent manner 154. IL‐27 is a cytokine produced by myeloid cells 155 and functions to inhibit HIV‐1 replication in various cell types 156, 157, 158. Whether BST‐2 is one of the effectors of anti‐HIV‐1 activity of IL‐27 is yet to be determined.…”

Interleukin-2 Inhibits HIV-1 Replication in Some Human T Cell Lymphotrophic Virus-1-infected Cell Lines via the Induction and Incorporation of APOBEC3G into the Virion

“…Rabbit polyclonal antibody to APOBEC3G and mouse monoclonal antibody to HIV-1 Vif were obtained from Abcam (Cambridge, MA). Peripheral blood mononuclear cells (PBMCs) were isolated from healthy donors by Ficoll-Hypaque centrifugation, as previously described (11). CD4 ϩ T cells were purified from PBMCs using CD4 microimmunomagnetic beads (Miltenyi Biotec, Auburn, CA) according to the manufacturer's instructions.…”

“…These include HLA-type (1)(2)(3)(4), HIV co-receptor expression (5), the cytidine deaminase APOBEC3G (6,7), tetherin (BST-2) (8), SAMHD1 (9,10), and an array of cytokines. Some cytokines such as type 1 and type 3 interferons, chemokines (e.g., stromal cell-derived factor 1, macrophage inflammatory factor 1a, RANTES (regulated on activation normal T cell expressed and secreted), and IL-27) inhibit HIV replication (11)(12)(13), whereas some enhance replication (IL-6 (14), tumor necrosis factor-␣ (15), IL-12 (16), and colony-stimulating factors (17,18)), and some are capable of either inhibiting or enhancing replication depending upon the culture system and conditions. In this regard, IL-2 has been shown to be capable of suppressing HIV-1 replication through the enhancement of CD8ϩ T cell function and enhancing HIV-1 replication in primary cultures of CD4ϩ T cells (19 -21).…”