Human Immunodeficiency Viruses: Propagation, Quantification, and Storage

Peters, Paul J.; Richards, Kathryn H.; Clapham, Paul R.

doi:10.1002/9780471729259.mc15j01s02

Cited by 3 publications

(2 citation statements)

References 35 publications

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“…After 48 hr, infected cells were lysed to measure luciferase activity using a commercial kit (Promega, E1500, Madison, WI). The 50% tissue culture infective dose (TCID50) was calculated using the “TCID” macro as described previously (Richards & Clapham, 2006 ).…”

Section: Methodsmentioning

confidence: 99%

Broad‐spectrum antiviral activity of Spatholobus suberectus Dunn against SARS‐CoV‐2, SARS‐CoV‐1, H5N1, and other enveloped viruses

Liu

Kwan

Cao

et al. 2022

Phytotherapy Research

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The current COVID‐19 pandemic caused by SARS‐Cov‐2 is responsible for more than 6 million deaths globally. The development of broad‐spectrum and cost‐effective antivirals is urgently needed. Medicinal plants are renowned as a complementary approach in which antiviral natural products have been established as safe and effective drugs. Here, we report that the percolation extract of Spatholobus suberectus Dunn (SSP) is a broad‐spectrum viral entry inhibitor against SARS‐CoV‐1/2 and other enveloped viruses. The viral inhibitory activities of the SSP were evaluated by using pseudotyped SARS‐CoV‐1 and 2, HIV‐1ADA and HXB2, and H5N1. SSP effectively inhibited viral entry and with EC50 values ranging from 3.6 to 5.1 μg/ml. Pre‐treatment of pseudovirus or target cells with SSP showed consistent inhibitory activities with the respective EC50 value of 2.3 or 2.1 μg/ml. SSP blocked both SARS‐CoV‐2 spike glycoprotein and the host ACE2 receptor. In vivo studies indicated that there was no abnormal toxicity and behavior in long‐term SSP treatment. Based on these findings, we concluded that SSP has the potential to be developed as a drug candidate for preventing and treating COVID‐19 and other emerging enveloped viruses.

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Section: Methodsmentioning

confidence: 99%

Broad‐spectrum antiviral activity of Spatholobus suberectus Dunn against SARS‐CoV‐2, SARS‐CoV‐1, H5N1, and other enveloped viruses

Liu

Kwan

Cao

et al. 2022

Phytotherapy Research

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“…Cell-free supernatant was collected 48 h posttransfection and frozen at Ϫ80°C. The 50% tissue culture infective dose (TCID 50 ) was calculated as described previously (35).…”

Section: Methodsmentioning

confidence: 99%

F18, a Novel Small-Molecule Nonnucleoside Reverse Transcriptase Inhibitor, Inhibits HIV-1 Replication Using Distinct Binding Motifs as Demonstrated by Resistance Selection and Docking Analysis

Liu

Zhang

et al. 2012

Antimicrob Agents Chemother

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Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are one of the key components of antiretroviral therapy drug regimen against human immunodeficiency virus type 1 (HIV-1) replication. We previously described a newly synthesized small molecule, 10-chloromethyl-11-demethyl-12-oxo-calanolide A (F18), a (؉)-calanolide A analog, as a novel anti-HIV-1 NNRTI (H. Xue et al., J. Med. Chem. 53:1397-1401, 2010). Here, we further investigated its antiviral range, drug resistance profile, and underlying mechanism of action. F18 consistently displayed potent activity against primary HIV-1 isolates, including various subtypes of group M, circulating recombinant form (CRF) 01_AE, and laboratory-adapted drug-resistant viruses. Moreover, F18 displayed distinct profiles against 17 NNRTI-resistant pseudoviruses, with an excellent potency especially against one of the most prevalent strains with the Y181C mutation (50% effective concentration, 1.0 nM), which was in stark contrast to the extensively used NNRTIs nevirapine and efavirenz. Moreover, we induced F18-resistant viruses by in vitro serial passages and found that the mutation L100I appeared to be the dominant contributor to F18 resistance, further suggesting a binding motif different from that of nevirapine and efavirenz. F18 was nonantagonistic when used in combination with other antiretrovirals against both wild-type and drug-resistant viruses in infected peripheral blood mononuclear cells. Interestingly, F18 displayed a highly synergistic antiviral effect with nevirapine against nevirapine-resistant virus (Y181C). Furthermore, in silico docking analysis suggested that F18 may bind to the HIV-1 reverse transcriptase differently from other NNRTIs. This study presents F18 as a new potential drug for clinical use and also presents a new mechanism-based design for future NNRTI.

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Inhibition of caspase pathways limits CD4+ T cell loss and restores host anti-retroviral function in HIV-1 infected humanized mice with augmented lymphoid tissue

Holloway,

Saito,

Naqvi

et al. 2024

Retrovirology

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The study of HIV infection and pathogenicity in physical reservoirs requires a biologically relevant model. The human immune system (HIS) mouse is an established model of HIV infection, but defects in immune tissue reconstitution remain a challenge for examining pathology in tissues. We utilized exogenous injection of the human recombinant FMS-like tyrosine kinase 3 ligand (rFLT-3 L) into the hematopoietic stem cell (HSC) cord blood HIS mouse model to significantly expand the total area of lymph node (LN) and the number of circulating human T cells. The results enabled visualization and quantification of HIV infectivity, CD4 T cell depletion and other measures of pathogenesis in the secondary lymphoid tissues of the spleen and LN. Treatment with the Caspase-1/4 inhibitor VX-765 limited CD4+ T cell loss in the spleen and reduced viral load in both the spleen and axillary LN. In situ hybridization further demonstrated a decrease in viral RNA in both the spleen and LN. Transcriptomic analysis revealed that in vivo inhibition of caspase-1/4 led to an upregulation in host HIV restriction factors including SAMHD1 and APOBEC3A. These findings highlight the use of rFLT-3 L to augment human immune system characteristics in HIS mice to support investigations of HIV pathogenesis and test host directed therapies, though further refinements are needed to further augment LN architecture and cellular populations. The results further provide in vivo evidence of the potential to target inflammasome pathways as an avenue of host-directed therapy to limit immune dysfunction and virus replication in tissue compartments of HIV+ persons.

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Human Immunodeficiency Viruses: Propagation, Quantification, and Storage

Cited by 3 publications

References 35 publications

Broad‐spectrum antiviral activity of Spatholobus suberectus Dunn against SARS‐CoV‐2, SARS‐CoV‐1, H5N1, and other enveloped viruses

Broad‐spectrum antiviral activity of Spatholobus suberectus Dunn against SARS‐CoV‐2, SARS‐CoV‐1, H5N1, and other enveloped viruses

F18, a Novel Small-Molecule Nonnucleoside Reverse Transcriptase Inhibitor, Inhibits HIV-1 Replication Using Distinct Binding Motifs as Demonstrated by Resistance Selection and Docking Analysis

Inhibition of caspase pathways limits CD4+ T cell loss and restores host anti-retroviral function in HIV-1 infected humanized mice with augmented lymphoid tissue

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