Leukocyte Filtration Removes Infectious Particulate Debris but Not Free Virus Derived from Experimentally Lysed HIV-Infected Cells

Vox Sanguinis ◽  
1991 ◽  
Vol 60 (4) ◽  
pp. 214-218
Author(s):  
Bhupat Rawal ◽  
T.S. Benedict Yen ◽  
Girish N. Vyas ◽  
Michael Busch
Keyword(s):  
Free Virus ◽  
Infected Cells ◽  
Particulate Debris ◽  
Leukocyte Filtration

Leukocyte Filtration Removes Infectious Particulate Debris but Not Free Virus Derived from Experimentally Lysed HIV-infected Cells

Vox Sanguinis ◽  
1991 ◽  
Vol 60 (4) ◽  
pp. 214-218 ◽  
Author(s):  
Bhupat Rawal ◽  
T. S. Benedict Yen ◽  
Girish N. Vyas ◽  
Michael Busch
Keyword(s):  
Free Virus ◽  
Infected Cells ◽  
Particulate Debris ◽  
Leukocyte Filtration

scholarly journals Zika virus is transmitted in neural progenitor cells via cell-to-cell spread and infection is inhibited by the autophagy inducer trehalose

2020 ◽  
pp. JVI.02024-20
Author(s):  
Alex E Clark ◽  
Zhe Zhu ◽  
Florian Krach ◽  
Jeremy N Rich ◽  
Gene W. Yeo ◽  
...  
Keyword(s):  
Viral Replication ◽  
Progenitor Cells ◽  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Neutralizing Antibody ◽  
Neural Progenitor ◽  
Health Concern ◽  
Free Virus ◽  
Zikv Infection ◽  
Infected Cells

Zika virus (ZIKV) is a mosquito-borne human pathogen that causes congenital Zika syndrome and neurological symptoms in some adults. There are currently no approved treatments or vaccines for ZIKV, and exploration of therapies targeting host processes could avoid viral development of drug resistance. The purpose of our study was to determine if the non-toxic and widely used disaccharide trehalose, which showed antiviral activity against Human Cytomegalovirus (HCMV) in our previous work, could restrict ZIKV infection in clinically relevant neural progenitor cells (NPCs). Trehalose is known to induce autophagy, the degradation and recycling of cellular components. Whether autophagy is proviral or antiviral for ZIKV is controversial and depends on cell type and specific conditions used to activate or inhibit autophagy. We show here that trehalose treatment of NPCs infected with recent ZIKV isolates from Panama and Puerto Rico significantly reduces viral replication and spread. In addition, we demonstrate that ZIKV infection in NPCs spreads primarily cell-to-cell as an expanding infectious center, and NPCs are infected via contact with infected cells far more efficiently than by cell-free virus. Importantly, ZIKV was able to spread in NPCs in the presence of neutralizing antibody.Importance Zika virus causes birth defects and can lead to neurological disease in adults. While infection rates are currently low, ZIKV remains a public health concern with no treatment or vaccine available. Targeting a cellular pathway to inhibit viral replication is a potential treatment strategy that avoids development of antiviral resistance. We demonstrate in this study that the non-toxic autophagy-inducing disaccharide trehalose reduces spread and output of ZIKV in infected neural progenitor cells (NPCs), the major cells infected in the fetus. We show that ZIKV spreads cell-to-cell in NPCs as an infectious center and that NPCs are more permissive to infection by contact with infected cells than by cell-free virus. We find that neutralizing antibody does not prevent the spread of the infection in NPCs. These results are significant in demonstrating anti-ZIKV activity of trehalose and in clarifying the primary means of Zika virus spread in clinically relevant target cells.

scholarly journals A universal dual mechanism immunotherapy for the treatment of influenza virus infections

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Liu ◽  
Boning Zhang ◽  
Yingcai Wang ◽  
Hanan S. Haymour ◽  
Fenghua Zhang ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza Pandemic ◽  
Intraperitoneal Administration ◽  
Neuraminidase Inhibitor ◽  
Virus Infections ◽  
Free Virus ◽  
Current Therapies ◽  
Severe Infections ◽  
Infected Cells ◽  
1918 Influenza

Abstract Seasonal influenza epidemics lead to 3–5 million severe infections and 290,000–650,000 annual global deaths. With deaths from the 1918 influenza pandemic estimated at >50,000,000 and future pandemics anticipated, the need for a potent influenza treatment is critical. In this study, we design and synthesize a bifunctional small molecule by conjugating the neuraminidase inhibitor, zanamivir, with the highly immunogenic hapten, dinitrophenyl (DNP), which specifically targets the surface of free virus and viral-infected cells. We show that this leads to simultaneous inhibition of virus release, and immune-mediated elimination of both free virus and virus-infected cells. Intranasal or intraperitoneal administration of a single dose of drug to mice infected with 100x MLD50 virus is shown to eradicate advanced infections from representative strains of both influenza A and B viruses. Since treatments of severe infections remain effective up to three days post lethal inoculation, our approach may successfully treat infections refractory to current therapies.

Inactivated Whole SIV Vaccine in Macaques: Evaluation of Protective Efficacy Against Challenge with Cell-Free Virus or Infected Cells

1992 ◽  
Vol 8 (8) ◽  
pp. 1501-1505 ◽  
Author(s):  
PHILIP R. JOHNSON ◽  
DAVID C. MONTEFIORI ◽  
SIMON GOLDSTEIN ◽  
TIFFANY E. HAMM ◽  
JIYING ZHOU ◽  
...  
Keyword(s):  
Protective Efficacy ◽  
Free Virus ◽  
Infected Cells

scholarly journals Infection of lymphoid tissues in the macaque upper respiratory tract contributes to the emergence of transmissible measles virus

2013 ◽  
Vol 94 (9) ◽  
pp. 1933-1944 ◽  
Author(s):  
Martin Ludlow ◽  
Rory D. de Vries ◽  
Ken Lemon ◽  
Stephen McQuaid ◽  
Emma Millar ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Respiratory Tract ◽  
Immune Cells ◽  
Measles Virus ◽  
Upper Respiratory Tract ◽  
Free Virus ◽  
Cell Debris ◽  
Cell Layers ◽  
Infected Cells ◽  
Upper Respiratory

Measles virus (MV), a member of the family Paramyxoviridae, remains a major cause of morbidity and mortality in the developing world. MV is spread by aerosols but the mechanism(s) responsible for the high transmissibility of MV are largely unknown. We previously infected macaques with enhanced green fluorescent protein-expressing recombinant MV and euthanized them at a range of time points. In this study a comprehensive pathological analysis has been performed of tissues from the respiratory tract around the peak of virus replication. Isolation of virus from nose and throat swab samples showed that high levels of both cell-associated and cell-free virus were present in the upper respiratory tract. Analysis of tissue sections from lung and primary bronchus revealed localized infection of epithelial cells, concomitant infiltration of MV-infected immune cells into the epithelium and localized shedding of cells or cell debris into the lumen. While high numbers of MV-infected cells were present in the tongue, these were largely encapsulated by intact keratinocyte cell layers that likely limit virus transmission. In contrast, the integrity of tonsillar and adenoidal epithelia was disrupted with high numbers of MV-infected epithelial cells and infiltrating immune cells present throughout epithelial cell layers. Disruption was associated with large numbers of MV-infected cells or cell debris ‘spilling’ from epithelia into the respiratory tract. The coughing and sneezing response induced by disruption of the ciliated epithelium, leading to the expulsion of MV-infected cells, cell debris and cell-free virus, contributes to the highly infectious nature of MV.

scholarly journals Autophagic flux without a block differentiates varicella-zoster virus infection from herpes simplex virus infection

2014 ◽  
Vol 112 (1) ◽  
pp. 256-261 ◽  
Author(s):  
Erin M. Buckingham ◽  
John E. Carpenter ◽  
Wallen Jackson ◽  
Leigh Zerboni ◽  
Ann M. Arvin ◽  
...  
Keyword(s):  
Virus Infection ◽  
Mouse Model ◽  
Infected Cell ◽  
Human Skin ◽  
Scid Mouse ◽  
Autophagic Flux ◽  
Free Virus ◽  
Varicella Zoster ◽  
Infected Cells ◽  
Scid Mouse Model

Autophagy is a process by which misfolded and damaged proteins are sequestered into autophagosomes, before degradation in and recycling from lysosomes. We have extensively studied the role of autophagy in varicella-zoster virus (VZV) infection, and have observed that vesicular cells are filled with >100 autophagosomes that are easily detectable after immunolabeling for the LC3 protein. To confirm our hypothesis that increased autophagosome formation was not secondary to a block, we examined all conditions of VZV infection as well as carrying out two assessments of autophagic flux. We first investigated autophagy in human skin xenografts in the severe combined immunodeficiency (SCID) mouse model of VZV pathogenesis, and observed that autophagosomes were abundant in infected human skin tissues. We next investigated autophagy following infection with sonically prepared cell-free virus in cultured cells. Under these conditions, autophagy was detected in a majority of infected cells, but was much less than that seen after an infected-cell inoculum. In other words, inoculation with lower-titered cell-free virus did not reflect the level of stress to the VZV-infected cell that was seen after inoculation of human skin in the SCID mouse model or monolayers with higher-titered infected cells. Finally, we investigated VZV-induced autophagic flux by two different methods (radiolabeling proteins and a dual-colored LC3 plasmid); both showed no evidence of a block in autophagy. Overall, therefore, autophagy within a VZV-infected cell was remarkably different from autophagy within an HSV-infected cell, whose genome contains two modifiers of autophagy, ICP34.5 and US11, not present in VZV.

scholarly journals The Peptide A-3302-B Isolated from a Marine Bacterium Micromonospora sp. Inhibits HSV-2 Infection by Preventing the Viral Egress from Host Cells

2022 ◽  
Vol 23 (2) ◽  
pp. 947
Author(s):  
Sanya Sureram ◽  
Irene Arduino ◽  
Reiko Ueoka ◽  
Massimo Rittà ◽  
Rachele Francese ◽  
...  
Keyword(s):  
Marine Bacterium ◽  
Host Cells ◽  
Drug Resistant ◽  
Free Virus ◽  
Viral Egress ◽  
Infected Cells ◽  
Simplex Virus ◽  
Replicative Cycle

Herpesviruses are highly prevalent in the human population, and frequent reactivations occur throughout life. Despite antiviral drugs against herpetic infections, the increasing appearance of drug-resistant viral strains and their adverse effects prompt the research of novel antiherpetic drugs for treating lesions. Peptides obtained from natural sources have recently become of particular interest for antiviral therapy applications. In this work, we investigated the antiviral activity of the peptide A-3302-B, isolated from a marine bacterium, Micromonospora sp., strain MAG 9-7, against herpes simplex virus type 1, type 2, and human cytomegalovirus. Results showed that the peptide exerted a specific inhibitory activity against HSV-2 with an EC50 value of 14 μM. Specific antiviral assays were performed to investigate the mechanism of action of A-3302-B. We demonstrated that the peptide did not affect the expression of viral proteins, but it inhibited the late events of the HSV-2 replicative cycle. In detail, it reduced the cell-to-cell virus spread and the transmission of the extracellular free virus by preventing the egress of HSV-2 progeny from the infected cells. The dual antiviral and previously reported anti-inflammatory activities of A-3302-B, and its effect against an acyclovir-resistant HSV-2 strain are attractive features for developing a therapeutic to reduce the transmission of HSV-2 infections.

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