Exploiting the exploiter: a viral inhibitor stabilizes TAP for cryo-EM

2016 ◽  
Vol 23 (2) ◽  
pp. 95-97 ◽  
Author(s):  
Rutger D Luteijn ◽  
Emmanuel J H J Wiertz
Keyword(s):  
Viral Inhibitor

Circulating interferon-like viral inhibitor in patients with meningitis due to H. influenzae

1965 ◽  
Vol 67 (5) ◽  
pp. 922-924
Author(s):  
Richard H. Michaels ◽  
Miles M. Weinberger ◽  
Monto Ho
Keyword(s):  
Viral Inhibitor

scholarly journals Mitochondrial Cell Death Suppressors Carried by Human and Murine Cytomegalovirus Confer Resistance to Proteasome Inhibitor-Induced Apoptosis

2005 ◽  
Vol 79 (19) ◽  
pp. 12205-12217 ◽  
Author(s):  
A. Louise McCormick ◽  
Christopher D. Meiering ◽  
Geoffrey B. Smith ◽  
Edward S. Mocarski
Keyword(s):  
Cell Death ◽  
Viral Genome ◽  
Proteasome Inhibitor ◽  
Proteasome Inhibition ◽  
Murine Cytomegalovirus ◽  
Viral Inhibitor ◽  
Infected Cells ◽  
Induced Apoptosis ◽  
Functional Copy ◽  
Inactivating Mutations

ABSTRACT Human cytomegalovirus carries a mitochondria-localized inhibitor of apoptosis (vMIA) that is conserved in primate cytomegaloviruses. We find that inactivating mutations within UL37x1, which encodes vMIA, do not substantially affect replication in TownevarATCC (Towne-BAC), a virus that carries a functional copy of the betaherpesvirus-conserved viral inhibitor of caspase 8 activation, the UL36 gene product. In Towne-BAC infection, vMIA reduces susceptibility of infected cells to intrinsic death induced by proteasome inhibition. vMIA is sufficient to confer resistance to proteasome inhibition when expressed independent of viral infection. Murine cytomegalovirus m38.5, whose position in the viral genome is analogous to UL37x1, exhibits mitochondrial association and functions in much the same manner as vMIA in inhibiting intrinsic cell death. This work suggests a common role for vMIA in rodent and primate cytomegaloviruses, modulating the threshold of virus-infected cells to intrinsic cell death.

vMIA, a viral inhibitor of apoptosis targeting mitochondria

Biochimie ◽  
2002 ◽  
Vol 84 (2-3) ◽  
pp. 177-185 ◽  
Author(s):  
Victor S Goldmacher
Keyword(s):  
Inhibitor Of Apoptosis ◽  
Viral Inhibitor

scholarly journals GROWTH CHARACTERISTICS OF INFLUENZA VIRUS

1955 ◽  
Vol 102 (4) ◽  
pp. 393-402 ◽  
Author(s):  
W. Wilbur Ackermann ◽  
Hunein F. Maassab
Keyword(s):  
Influenza Virus ◽  
Latent Period ◽  
Growth Curve ◽  
Chorioallantoic Membrane ◽  
Growth Characteristics ◽  
Stages Of Development ◽  
Viral Inhibitor ◽  
Site Of Action ◽  
Two Stages

A further analysis of the growth curve obtained in vitro for influenza virus in chorioallantoic membrane has been made using the viral inhibitor p-fluorophenylalanine. It has been found that p-fluorophenylalanine is phase-specific, does not interfere with the initiation of infection but rather acts during the productive period of the infectious sequence. The site of action of this fluoroderivative has been described relative to the site of action of methoxinine. By the use of this inhibitor in combination with methoxinine, it has been possible to recognize two stages of development which were not discernible from the usual growth curve. In a multicellular culture these two reactions, A and B, occur for the most part simultaneously, during the latent and productive periods. Reaction A is inhibited by methoxinine, but not by fluorophenylalanine. It begins early in the latent period and can proceed independent of reaction B. Reaction B is inhibited by fluorophenylalanine, but not by methoxinine, and it cannot proceed unless reaction A is proceeding or has operated for some prior interval.

scholarly journals The Many Faces of the Flavivirus NS5 Protein in Antagonism of Type I Interferon Signaling

2016 ◽  
Vol 91 (3) ◽  
Author(s):  
Sonja M. Best
Keyword(s):  
Type I Interferon ◽  
Important Determinant ◽  
Nonstructural Protein ◽  
Severe Disease ◽  
Type I ◽  
Interferon Signaling ◽  
Antiviral Effects ◽  
Viral Inhibitor ◽  
Vector Borne ◽  
The Many

ABSTRACT The vector-borne flaviviruses cause severe disease in humans on every inhabited continent on earth. Their transmission by arthropods, particularly mosquitoes, facilitates large emergence events such as witnessed with Zika virus (ZIKV) or West Nile virus in the Americas. Every vector-borne flavivirus examined thus far that causes disease in humans, from dengue virus to ZIKV, antagonizes the host type I interferon (IFN-I) response by preventing JAK-STAT signaling, suggesting that suppression of this pathway is an important determinant of infection. The most direct and potent viral inhibitor of this pathway is the nonstructural protein NS5. However, the mechanisms utilized by NS5 from different flaviviruses are often quite different, sometimes despite close evolutionary relationships between viruses. The varied mechanisms of NS5 as an IFN-I antagonist are also surprising given that the evolution of NS5 is restrained by the requirement to maintain function of two enzymatic activities critical for virus replication, the methyltransferase and RNA-dependent RNA polymerase. This review discusses the different strategies used by flavivirus NS5 to evade the antiviral effects of IFN-I and how this information can be used to better model disease and develop antiviral countermeasures.

scholarly journals 25-Hydroxycholesterol-Conjugated EK1 Peptide with Potent and Broad-Spectrum Inhibitory Activity against SARS-CoV-2, Its Variants of Concern, and Other Human Coronaviruses

2021 ◽  
Vol 22 (21) ◽  
pp. 11869
Author(s):  
Qiaoshuai Lan ◽  
Chao Wang ◽  
Jie Zhou ◽  
Lijue Wang ◽  
Fanke Jiao ◽  
...  
Keyword(s):  
Public Health ◽  
Antiviral Activity ◽  
Broad Spectrum ◽  
Fusion Inhibitor ◽  
Global Public Health ◽  
Newborn Mice ◽  
Viral Inhibitor ◽  
Modified Peptides ◽  
Human Coronaviruses ◽  
Enzymatic Product

The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to global public health and the economy. The enzymatic product of cholesterol 25-hydroxylase (CH25H), 25-Hydroxycholesterol (25-HC), was reported to have potent anti-SARS-CoV-2 activity. Here, we found that the combination of 25-HC with EK1 peptide, a pan-coronavirus (CoV) fusion inhibitor, showed a synergistic antiviral activity. We then used the method of 25-HC modification to design and synthesize a series of 25-HC-modified peptides and found that a 25-HC-modified EK1 peptide (EK1P4HC) was highly effective against infections caused by SARS-CoV-2, its variants of concern (VOCs), and other human CoVs, such as HCoV-OC43 and HCoV-229E. EK1P4HC could protect newborn mice from lethal HCoV-OC43 infection, suggesting that conjugation of 25-HC with a peptide-based viral inhibitor was a feasible and universal strategy to improve its antiviral activity.

scholarly journals Cell-produced viral inhibitor: possible mechanism of action and chemical composition.

1981 ◽  
Vol 32 (2) ◽  
pp. 454-457 ◽  
Author(s):  
T K Hughes ◽  
J E Blalock ◽  
M L McKerlie ◽  
S Baron
Keyword(s):  
Chemical Composition ◽  
Mechanism Of Action ◽  
Viral Inhibitor

scholarly journals Multiple Autonomous Cell Death Suppression Strategies Ensure Cytomegalovirus Fitness

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1707
Author(s):  
Pratyusha Mandal ◽  
Lynsey N. Nagrani ◽  
Liliana Hernandez ◽  
Anita Louise McCormick ◽  
Christopher P. Dillon ◽  
...  
Keyword(s):  
Cell Death ◽  
Murine Cytomegalovirus ◽  
Mammalian Host ◽  
Caspase 8 ◽  
Intrinsic Apoptosis ◽  
Pathogen Invasion ◽  
Cell Death Pathways ◽  
Viral Inhibitor ◽  
Extrinsic Apoptosis ◽  
Infected Cells

Programmed cell death pathways eliminate infected cells and regulate infection-associated inflammation during pathogen invasion. Cytomegaloviruses encode several distinct suppressors that block intrinsic apoptosis, extrinsic apoptosis, and necroptosis, pathways that impact pathogenesis of this ubiquitous herpesvirus. Here, we expanded the understanding of three cell autonomous suppression mechanisms on which murine cytomegalovirus relies: (i) M38.5-encoded viral mitochondrial inhibitor of apoptosis (vMIA), a BAX suppressor that functions in concert with M41.1-encoded viral inhibitor of BAK oligomerization (vIBO), (ii) M36-encoded viral inhibitor of caspase-8 activation (vICA), and (iii) M45-encoded viral inhibitor of RIP/RHIM activation (vIRA). Following infection of bone marrow-derived macrophages, the virus initially deflected receptor-interacting protein kinase (RIPK)3-dependent necroptosis, the most potent of the three cell death pathways. This process remained independent of caspase-8, although suppression of this apoptotic protease enhances necroptosis in most cell types. Second, the virus deflected TNF-mediated extrinsic apoptosis, a pathway dependent on autocrine TNF production by macrophages that proceeds independently of mitochondrial death machinery or RIPK3. Third, cytomegalovirus deflected BCL-2 family protein-dependent mitochondrial cell death through combined TNF-dependent and -independent signaling even in the absence of RIPK1, RIPK3, and caspase-8. Furthermore, each of these cell death pathways dictated a distinct pattern of cytokine and chemokine activation. Therefore, cytomegalovirus employs sequential, non-redundant suppression strategies to specifically modulate the timing and execution of necroptosis, extrinsic apoptosis, and intrinsic apoptosis within infected cells to orchestrate virus control and infection-dependent inflammation. Virus-encoded death suppressors together hold control over an intricate network that upends host defense and supports pathogenesis in the intact mammalian host.

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