Efficient transmission and persistence of low‐frequency SIVmac251 variants in CD8-depleted rhesus macaques with different neuropathology

Infection of CD8-depleted rhesus macaques with the genetically heterogeneous simian immunodeficiency virus (SIV)mac251 viral swarm provides a rapid-disease model for simian acquired immune deficiency syndrome and SIV-encephalitis (SIVE). The objective was to evaluate how the diversity of the swarm influences the initial seeding of the infection that may potentially affect disease progression. Plasma, lymphoid and non-lymphoid (brain and lung) tissues were collected from two infected macaques euthanized at 21 days post-infection (p.i.), as well as longitudinal specimens and post-mortem tissues from four macaques followed throughout the infection. About 1300 gp120 viral sequences were obtained from the infecting SIVmac251 swarm and the macaques longitudinal and post-mortem samples. Phylogenetic and amino acid signature pattern analyses were carried out to assess frequency, transmission dynamics and persistence of specific viral clusters. Although no significant reduction in viral heterogeneity was found early in infection (21 days p.i.), transmission and replication of SIV variants was not entirely random. In particular, two distinct motifs under-represented (<4 %) in the infecting swarm were found at high frequencies (up to 14 %) in all six macaques as early as 21 days p.i. Moreover, a macrophage tropic variant not detected in the viral swarm (<0.3 %) was present at high frequency (29–100 %) in sequences derived from the brain of two macaques with meningitis or severe SIVE. This study demonstrates the highly efficient transmission and persistence in vivo of multiple low frequency SIVmac251 founder variants, characterized by specific gp120 motifs that may be linked to pathogenesis in the rapid-disease model of neuroAIDS.

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A Critical Review of the Evidence Concerning the HIV Latency Reversing Effect of Disulfiram, the Possible Explanations for Its Inability to Reduce the Size of the Latent Reservoir In Vivo, and the Caveats Associated with Its Use in Practice

AIDS Research and Treatment ◽

10.1155/2017/8239428 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Harry D. J. Knights

Keyword(s):

Immune Deficiency Syndrome ◽

Deficiency Syndrome ◽

Latent Reservoir ◽

Major Barrier ◽

Latently Infected ◽

Shock And Kill ◽

Infected Cells ◽

Hiv 1

Combination antiretroviral therapy (cART) effectively suppresses the replication of human immunodeficiency virus type 1 (HIV-1), improves immune function, and decreases the morbidity of acquired immune deficiency syndrome (AIDS). However, it is unable to eradicate the virus because it does not eliminate latently infected cells. The latent reservoir poses the major barrier to an HIV-1 cure. The “shock and kill” strategy aims to reactivate the virus and destroy latently infected cells. Many latency reversing agents (LRAs) reactivate HIV in vitro, but the absence of damaging side-effects and efficacy in vivo make disulfiram particularly promising. However, in clinical trials to date, disulfiram treatment has not resulted in a reduction in the size of the latent reservoir. In this article I will therefore discuss the evidence for the latency reversing effect of disulfiram, the possible explanations for its inability to reduce the size of the latent reservoir in vivo, and the caveats associated with its use in practice. These considerations will help to inform judgements about the prospect of an HIV cure from disulfiram based treatments.

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Cross-species transmission and recombination of ‘AIDS’ viruses

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.1995.0089 ◽

1995 ◽

Vol 349 (1327) ◽

pp. 41-47 ◽

Cited By ~ 62

Keyword(s):

Vaccine Development ◽

Phylogenetic Analyses ◽

Immune Deficiency Syndrome ◽

Deficiency Syndrome ◽

Biological Properties ◽

Hiv Vaccine ◽

Human Immunodeficiency Viruses ◽

Acquired Immune Deficiency ◽

Hiv 1

Acquired Immune Deficiency Syndrome (AIDS) is caused by two different Human Immunodeficiency Viruses, HIV-1 and HIV-2. Closely related viruses (SIVs) are found in many species of non-human primates. Phylogenetic analyses indicate that cross-species transmission events have been quite frequent. Both HIV-1 and HIV-2 appear to have resulted from multiple transfers of lentiviruses naturally infecting other primates; the source of HIV-2 appears to have been sooty mangabeys, whereas for HIV-1 the source may have been chimpanzees. Phylogenetic analyses also provide evidence that recombination has occurred between divergent viruses in vivo . Evolutionary trees based on various regions of the viral genome generally have consistent branching orders. However, some isolates fall into significantly different phylogenetic positions, indicating that their genomes are mosaics of sequences with different evolutionary histories. This implies that co-infection with highly divergent viral strains can occur in HIV-infected humans and SIV-infected primates; this could lead to the generation of hybrid genomes with significantly altered biological properties, and also has important implications for HIV vaccine development programmes.

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The Interactions between the Antimicrobial Peptide P-113 and Living Candida albicans Cells Shed Light on Mechanisms of Antifungal Activity and Resistance

International Journal of Molecular Sciences ◽

10.3390/ijms21072654 ◽

2020 ◽

Vol 21 (7) ◽

pp. 2654 ◽

Cited By ~ 2

Author(s):

Kuang-Ting Cheng ◽

Chih-Lung Wu ◽

Bak-Sau Yip ◽

Ya-Han Chih ◽

Kuang-Li Peng ◽

...

Keyword(s):

Candida Albicans ◽

Antifungal Activity ◽

Antimicrobial Peptide ◽

Oral Candidiasis ◽

Immune Deficiency Syndrome ◽

Deficiency Syndrome ◽

Salivary Protein ◽

Histatin 5 ◽

C Terminus

In the absence of proper immunity, such as in the case of acquired immune deficiency syndrome (AIDS) patients, Candida albicans, the most common human fungal pathogen, may cause mucosal and even life-threatening systemic infections. P-113 (AKRHHGYKRKFH), an antimicrobial peptide (AMP) derived from the human salivary protein histatin 5, shows good safety and efficacy profiles in gingivitis and human immunodeficiency virus (HIV) patients with oral candidiasis. However, little is known about how P-113 interacts with Candida albicans or its degradation by Candida-secreted proteases that contribute to the fungi’s resistance. Here, we use solution nuclear magnetic resonance (NMR) methods to elucidate the molecular mechanism of interactions between P-113 and living Candida albicans cells. Furthermore, we found that proteolytic cleavage of the C-terminus prevents the entry of P-113 into cells and that increasing the hydrophobicity of the peptide can significantly increase its antifungal activity. These results could help in the design of novel antimicrobial peptides that have enhanced stability in vivo and that can have potential therapeutic applications.

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The Envelope Glycoprotein Ectodomains Determine the Efficiency of CD4+ T Lymphocyte Depletion in Simian– Human Immunodeficiency Virus–Infected Macaques

Journal of Experimental Medicine ◽

10.1084/jem.188.6.1159 ◽

1998 ◽

Vol 188 (6) ◽

pp. 1159-1171 ◽

Cited By ~ 89

Author(s):

Gunilla B. Karlsson ◽

Matilda Halloran ◽

Dominik Schenten ◽

Juliette Lee ◽

Paul Racz ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Lymphocytes ◽

T Lymphocyte ◽

Envelope Glycoprotein ◽

Rhesus Macaques ◽

Immune Deficiency Syndrome ◽

Lymphocyte Depletion ◽

Immunodeficiency Virus ◽

Hiv 1

CD4+ T lymphocyte depletion in human immunodeficiency virus type 1 (HIV-1)–infected humans underlies the development of acquired immune deficiency syndrome. Using a model in which rhesus macaques were infected with chimeric simian–human immunodeficiency viruses (SHIVs), we show that both the level of viremia and the structure of the HIV-1 envelope glycoprotein ectodomains individually contributed to the efficiency with which CD4+ T lymphocytes were depleted. The envelope glycoproteins of recombinant SHIVs that efficiently caused loss of CD4+ T lymphocytes exhibited increased chemokine receptor binding and membrane-fusing capacity compared with those of less pathogenic viruses. These studies identify the HIV-1 envelope glycoprotein ectodomains as determinants of CD4+ T lymphocyte loss in vivo and provide a foundation for studying pathogenic mechanisms.

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Traditional Chinese Medicine etiology and pathogenesis of acquired immune deficiency syndrome in simian immunodeficiency virus-infected Chinese rhesus macaques

Journal of Traditional Chinese Medicine ◽

10.1016/s0254-6272(13)60079-5 ◽

2012 ◽

Vol 32 (4) ◽

pp. 609-615 ◽

Cited By ~ 1

Author(s):

Maoqing Li ◽

Linchun Fu ◽

Yinjie Hu ◽

Miaomiao Zhang ◽

Jinyang He ◽

...

Keyword(s):

Immune Deficiency ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Rhesus Macaques ◽

Immune Deficiency Syndrome ◽

Acquired Immune Deficiency Syndrome ◽

Deficiency Syndrome ◽

Immunodeficiency Virus ◽

Chinese Rhesus Macaques ◽

Acquired Immune Deficiency

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Platelet Release in Hemophilia

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651119 ◽

1987 ◽

Vol 57 (03) ◽

pp. 294-297 ◽

Cited By ~ 5

Author(s):

Hamid Al-Mondhiry

Keyword(s):

Immune Deficiency ◽

Immune Deficiency Syndrome ◽

Deficiency Syndrome ◽

Severe Form ◽

Human Immune Deficiency Virus ◽

Marked Rise ◽

Platelet Factor ◽

Plasma Factor ◽

Platelet Release

SummaryPlatelet function abnormalities have been described in some patients with hemophilia. This study reports measurements of plasma β-thromboglobulin (BTG) and platelet factor 4 (PF4), sensitive and specific markers of platelet α-granule release in 72 hemophiliacs. Patients were studied on multiple occasions depending on their clinical condition and the treatment given. Stable patients without recent bleeding showed significantly elevated BTG levels: 29.72 ± 12.77 ng/ml, control 23.22 ± 8.22, p = 0.006. This appears to be independent of the presence of liver disease, human immune deficiency virus infection (HIV) and the acquired immune deficiency syndrome (AIDS). The increased BTG level seems to correlate with the severity of the disease as reflected by the frequency of bleeding and the quantity of factor concentrate used but not with plasma factor VIII or IX procoagulant activity. Patients who have experienced recent bleeding showed a marked rise in BTG level (77.26 ± 51.37 ng/ml, p = 0.0002), indicating enhanced in vivo platelet activation. These observations suggest that enhanced platelet release in hemophilia most likely reflects sustained activation of hemostasis secondary to frequent bleeding characteristic of the severe form of the disease.

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Artificial Stem Cells Mediated Inflammation-Tropic Delivery of Antiviral Drugs for Pneumonia Treatment

10.21203/rs.3.rs-1046275/v1 ◽

2021 ◽

Author(s):

Aiping Qin ◽

Sheng Chen ◽

Songpei Li ◽

Xiaotao Huang ◽

Yinshan Lin ◽

...

Keyword(s):

Stem Cells ◽

Synergistic Effects ◽

Immune Deficiency Syndrome ◽

Deficiency Syndrome ◽

Antiviral Drugs ◽

Viral Dna ◽

Marrow Mesenchymal Stem Cells ◽

Low Efficiency

Abstract Background: Cytomegalovirus (CMV) pneumonia is a major cause of morbidity and mortality in immunodeficiency individuals including transplant recipients and Acquired Immune Deficiency Syndrome patients. Currently, antiviral drugs ganciclovir (GCV) and phosphonoformate (PFA) are first-line agents for pneumonia caused by herpesvirus infection. However, the therapy suffers from various limitations such as low efficiency, drug resistance, toxicity, and lack of specificity.Methods: The antiviral drugs GCV and PFA were loaded into the pH-responsive nanoparticles fabricated by poly(lactic-co-glycolic acid) (PLGA) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and further coated with cell membranes derived from bone marrow mesenchymal stem cells to form artificial stem cells, namely MPDGP. We evaluated the viral suppression effects of MPDGP in vitro and in vivo.Results: MPDGP showed significant inflammation tropism and efficient suppression of both viral replication and virus infection-associated inflammation in the CMV-induced pneumonia model. The synergistic effects by combination of viral DNA elongation inhibitor GCV and viral DNA polymerase inhibitor PFA on suppressing the inflammation efficiently. Conclusion: The present study develops a novel therapeutic intervention using artificial stem cells to deliver antiviral drugs at inflammatory sites, which shows great potential for the targeted treatment of pneumonia. To our best knowledge, we are the first to fabricate this kind of artificial stem cells to deliver the antiviral drugs for pneumonia treatment.

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