Inhibition of Human Immunodeficiency Virus Replication and Growth Advantage of CD4+T Cells from HIV-Infected Individuals That Express Intracellular Antibodies Against HIV-1 gp120 or Tat

ABSTRACT Activation of RNase L by 2′,5′-linked oligoadenylates (2-5A) is one of the antiviral pathways of interferon action. To determine the involvement of the 2-5A system in the control of human immunodeficiency virus type 1 (HIV-1) replication, a segment of the HIV-1nef gene was replaced with human RNase L cDNA. HIV-1 provirus containing sense orientation RNase L cDNA caused increased expression of RNase L and 500- to 1,000-fold inhibition of virus replication in Jurkat cells for a period of about 2 weeks. Subsequently, a partial deletion of the RNase L cDNA which coincided with increases in virus production occurred. The anti-HIV activity of RNase L correlated with decreases in HIV-1 RNA and with an acceleration in cell death accompanied by DNA fragmentation. Replication of HIV-1 encoding RNase L was also transiently suppressed in peripheral blood lymphocytes (PBL). In contrast, recombinant HIV containing reverse orientation RNase L cDNA caused decreased levels of RNase L, increases in HIV yields, and reductions in the anti-HIV effect of alpha interferon in PBL and in Jurkat cells. To obtain constitutive and continuous expression of RNase L cDNA, Jurkat cells were cotransfected with HIV-1 proviral DNA and with plasmid containing a cytomegalovirus promoter driving expression of RNase L cDNA. The RNase L plasmid suppressed HIV-1 replication by eightfold, while an antisense RNase L construct enhanced virus production by twofold. These findings demonstrate that RNase L can severely impair HIV replication and suggest involvement of the 2-5A system in the anti-HIV effect of alpha interferon.

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Conformation of HIV-1 Envelope Governs Rhesus CD4 Usage and Simian-Human Immunodeficiency Virus Replication

mBio ◽

10.1128/mbio.02752-21 ◽

2022 ◽

Author(s):

Geraldine Vilmen ◽

Anna C. Smith ◽

Hector Cervera Benet ◽

Rajni Kant Shukla ◽

Ross C. Larue ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Animal Model ◽

Virus Replication ◽

Rhesus Macaques ◽

Envelope Glycoproteins ◽

Human Immunodeficiency Virus Replication ◽

Preclinical Testing ◽

Immunodeficiency Virus ◽

Human Immunodeficiency Viruses ◽

Hiv 1

Rhesus macaques are a critical animal model for preclinical testing of HIV-1 vaccine and prevention approaches. However, HIV-1 does not replicate in rhesus macaques, and thus, chimeric simian-human immunodeficiency viruses (SHIVs), which encode HIV-1 envelope glycoproteins (Envs), are used as surrogate challenge viruses to infect rhesus macaques for modeling HIV-1 infection.

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RevM10-expressing T cells derived in vivo from transduced human hematopoietic stem-progenitor cells inhibit human immunodeficiency virus replication.

Journal of Virology ◽

10.1128/jvi.71.6.4707-4716.1997 ◽

1997 ◽

Vol 71 (6) ◽

pp. 4707-4716 ◽

Cited By ~ 70

Author(s):

M L Bonyhadi ◽

K Moss ◽

A Voytovich ◽

J Auten ◽

C Kalfoglou ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Progenitor Cells ◽

Virus Replication ◽

Human Immunodeficiency Virus Replication ◽

Hematopoietic Stem ◽

Immunodeficiency Virus

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Alpha Interferon Potently Enhances the Anti-Human Immunodeficiency Virus Type 1 Activity of APOBEC3G in Resting Primary CD4 T Cells

Journal of Virology ◽

10.1128/jvi.00206-06 ◽

2006 ◽

Vol 80 (15) ◽

pp. 7645-7657 ◽

Cited By ~ 107

Author(s):

Keyang Chen ◽

Jialing Huang ◽

Chune Zhang ◽

Sophia Huang ◽

Giuseppe Nunnari ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Innate Immunity ◽

T Cells ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Cd4 T Cells ◽

Immunodeficiency Virus ◽

Anti Hiv ◽

Hiv 1

ABSTRACT The interferon (IFN) system, including various IFNs and IFN-inducible gene products, is well known for its potent innate immunity against wide-range viruses. Recently, a family of cytidine deaminases, functioning as another innate immunity against retroviral infection, has been identified. However, its regulation remains largely unknown. In this report, we demonstrate that through a regular IFN-α/β signal transduction pathway, IFN-α can significantly enhance the expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) in human primary resting but not activated CD4 T cells and the amounts of APOBEC3G associated with a low molecular mass. Interestingly, short-time treatments of newly infected resting CD4 T cells with IFN-α will significantly inactivate human immunodeficiency virus type 1 (HIV-1) at its early stage. This inhibition can be counteracted by APOBEC3G-specific short interfering RNA, indicating that IFN-α-induced APOBEC3G plays a key role in mediating this anti-HIV-1 process. Our data suggest that APOBEC3G is also a member of the IFN system, at least in resting CD4 T cells. Given that the IFN-α/APOBEC3G pathway has potent anti-HIV-1 capability in resting CD4 T cells, augmentation of this innate immunity barrier could prevent residual HIV-1 replication in its native reservoir in the post-highly active antiretroviral therapy era.

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Productive Infection of Plasmacytoid Dendritic Cells with Human Immunodeficiency Virus Type 1 Is Triggered by CD40 Ligation

Journal of Virology ◽

10.1128/jvi.76.21.11033-11041.2002 ◽

2002 ◽

Vol 76 (21) ◽

pp. 11033-11041 ◽

Cited By ~ 90

Author(s):

Lawrence Fong ◽

Manuela Mengozzi ◽

Nancy W. Abbey ◽

Brian G. Herndier ◽

Edgar G. Engleman

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Dendritic Cells ◽

Viral Replication ◽

Cd4 T Cells ◽

Cd40 Ligand ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Immature plasmacytoid dendritic cells are the principal alpha interferon-producing cells (IPC), responsible for primary antiviral immunity. IPC express surface molecules CD4, CCR5, and CXCR4, which are known coreceptors required for human immunodeficiency virus (HIV) infection. Here we show that IPC are susceptible to and replicate HIV type 1 (HIV-1). Importantly, viral replication is triggered upon activation of IPC with CD40 ligand, a signal physiologically delivered by CD4 T cells. Immunohistochemical staining of tonsil from HIV-infected individuals reveals HIV p24+ IPC, consistent with in vivo infection of these cells. IPC exposed in vitro to HIV produce alpha interferon, which partially inhibits viral replication. Nevertheless, IPC efficiently transmit HIV-1 to CD4 T-cells, and such transmission is also augmented by CD40 ligand activation. IPC produce RANTES/CCL5 and MIP-1α/CCL3 when exposed to HIV in vitro. IPC also induce naïve CD4 T cells to proliferate and would therefore preferentially infect these cells. These results indicate that IPC may play an important role in the dissemination of HIV.

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Naive CD4+ T Cells Harbor a Large Inducible Reservoir of Latent, Replication-competent Human Immunodeficiency Virus Type 1

Clinical Infectious Diseases ◽

10.1093/cid/ciz108 ◽

2019 ◽

Vol 69 (11) ◽

pp. 1919-1925 ◽

Cited By ~ 22

Author(s):

Jennifer M Zerbato ◽

Deborah K McMahon ◽

Michelle D Sobolewski ◽

John W Mellors ◽

Nicolas Sluis-Cremer

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Cd4 T Cells ◽

Virus Production ◽

Major Barrier ◽

Immunodeficiency Virus ◽

Hiv 1

Abstract Background The latent human immunodeficiency virus type 1 (HIV-1) reservoir represents a major barrier to a cure. Based on the levels of HIV-1 DNA in naive (TN) vs resting memory CD4+ T cells, it is widely hypothesized that this reservoir resides primarily within memory cells. Here, we compared virus production from TN and central memory (TCM) CD4+ T cells isolated from HIV-1–infected individuals on suppressive therapy. Methods CD4+ TN and TCM cells were purified from the blood of 7 HIV-1–infected individuals. We quantified total HIV-1 DNA in the CD4+ TN and TCM cells. Extracellular virion-associated HIV-1 RNA or viral outgrowth assays were used to assess latency reversal following treatment with anti-CD3/CD28 monoclonal antibodies (mAbs), phytohaemagglutinin/interleukin-2, phorbol 12-myristate 13-acetate/ionomycin, prostratin, panobinostat, or romidepsin. Results HIV-1 DNA was significantly higher in TCM compared to TN cells (2179 vs 684 copies/106 cells, respectively). Following exposure to anti-CD3/CD28 mAbs, virion-associated HIV-1 RNA levels were similar between TCM and TN cells (15 135 vs 18 290 copies/mL, respectively). In 4/7 donors, virus production was higher for TN cells independent of the latency reversing agent used. Replication-competent virus was recovered from both TN and TCM cells. Conclusions Although the frequency of HIV-1 infection is lower in TN compared to TCM cells, as much virus is produced from the TN population after latency reversal. This finding suggests that quantifying HIV-1 DNA alone may not predict the size of the inducible latent reservoir and that TN cells may be an important reservoir of latent HIV-1.

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Preferential Infection of α4β7+ Memory CD4+ T Cells During Early Acute Human Immunodeficiency Virus Type 1 Infection

Clinical Infectious Diseases ◽

10.1093/cid/ciaa497 ◽

2020 ◽

Vol 71 (11) ◽

pp. e735-e743 ◽

Cited By ~ 4

Author(s):

Andrey Tokarev ◽

Lyle R McKinnon ◽

Amélie Pagliuzza ◽

Aida Sivro ◽

Tosin E Omole ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Cd4 T Cells ◽

Acute Infection ◽

Immunodeficiency Virus ◽

Memory Cd4 T Cells ◽

Hiv 1

Abstract Background Establishment of persistent human immunodeficiency virus type 1 (HIV-1) reservoirs occurs early in infection, and biomarkers of infected CD4+ T cells during acute infection are poorly defined. CD4+ T cells expressing the gut homing integrin complex α4β7 are associated with HIV-1 acquisition, and are rapidly depleted from the periphery and gastrointestinal mucosa during acute HIV-1 infection. Methods Integrated HIV-1 DNA was quantified in peripheral blood mononuclear cells obtained from acutely (Fiebig I–III) and chronically infected individuals by sorting memory CD4+ T-cell subsets lacking or expressing high levels of integrin β7 (β7negative and β7high, respectively). HIV-1 DNA was also assessed after 8 months of combination antiretroviral therapy (cART) initiated in Fiebig II/III individuals. Activation marker and chemokine receptor expression was determined for β7-defined subsets at acute infection and in uninfected controls. Results In Fiebig I, memory CD4+ T cells harboring integrated HIV-1 DNA were rare in both β7high and β7negative subsets, with no significant difference in HIV-1 DNA copies. In Fiebig stages II/III and in chronically infected individuals, β7high cells were enriched in integrated and total HIV-1 DNA compared to β7negative cells. During suppressive cART, integrated HIV-1 DNA copies decreased in both β7negative and β7high subsets, which did not differ in DNA copies. In Fiebig II/III, integrated HIV-1 DNA in β7high cells was correlated with their activation. Conclusions β7high memory CD4+ T cells are preferential targets during early HIV-1 infection, which may be due to the increased activation of these cells.

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