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Length and density of α2-3 sialyllactose-containing chains on glycopolymers determine receptor binding of avian influenza viruses.

Influenza A viruses use host sialoglycans for attachment via hemagglutinin (HA) and hydrolyze them upon budding via neuraminidase (NA). The HAs of some human isolates prefer extended and branched glycans for binding; however, the preference of avian influenza viruses (AIVs) for these glycans is poorly understood. This study addressed the glycan-binding preferences of HA and AIV particles by using a series of sialoglycopolymers with various glycan representations and densities. Glycan extension was mimicked by linking the terminal sialyllactose with subsequent polyethylene glycol chains, and gl

Glycosaminoglycan binding by arboviruses: a cautionary tale.

Arboviruses are medically important arthropod-borne viruses that cause a range of diseases in humans from febrile illness to arthritis, encephalitis and hemorrhagic fever. Given their transmission cycles, these viruses face the challenge of replicating in evolutionarily divergent organisms that can include ticks, flies, mosquitoes, birds, rodents, reptiles and primates. Furthermore, their cell attachment receptor utilization may be affected by the opposing needs for generating high and sustained serum viremia in vertebrates such that virus particles are efficiently collected during a hematopha

Diazadispiroalkane Derivatives Are New Viral Entry Inhibitors.

Herpesviruses are widespread and can cause serious illness. Many currently available antiviral drugs have limited effects, result in rapid development of resistance, and often exhibit dose-dependent toxicity. Especially for human cytomegalovirus (HCMV), new well-tolerated compounds with novel mechanisms of action are urgently needed. In this study, we characterized the antiviral activity of two new diazadispiroalkane derivatives, 11826091 and 11826236. These two small molecules exhibited strong activity against low-passage-number HCMV. Pretreatment of cell-free virus with these compounds great

Extended receptor repertoire of an adenovirus associated with human obesity.

Human adenovirus type 36 (HAdV-D36) has been putatively linked to obesity in animals and has been associated with obesity in humans in some but not all studies. Despite extensive epidemiological research there is limited information about its receptor profile. We investigated the receptor portfolio of HAdV-D36 using a combined structural biology and virology approach. The HAdV-D36 fiber knob domain (FK), which mediates the primary attachment of many HAdVs to host cells, has a significantly elongated DG loop that alters known binding interfaces for established adenovirus receptors such as the c

The attachment factors and attachment receptors of human noroviruses.

Human noroviruses (HuNoVs) are the leading etiological agent causing the worldwide outbreaks of acute epidemic non-bacterial gastroenteritis. Histo-blood group antigens (HBGAs) are commonly acknowledged as cellular receptors or co-receptors for HuNoVs. However, certain genotypes of HuNoVs cannot bind with any HBGAs, suggesting potential additional co-factors and attachment receptors have not been identified yet. In addition, food items, such as oysters and lettuce, play an important role in the transmission of HuNoVs. In the past decade, a couple of attachment factors other than HBGAs have bee

Уроки, извлеченные из аденовируса (1970 - 2019 годы).

Животные вирусы хорошо известны своей способностью обнаруживать фундаментальные клеточные и молекулярные процессы, и аденовирус, несомненно, является наглядным примером. Этот обзор иллюстрирует уроки, извлеченные из изучения аденовируса за последние пять десятилетий. Мы взглянем на ключевые исследования структуры аденовирусов и биофизических свойств, которые выявили механизмы аденовирусной связи с антителами, рецепторами клеток и иммунными молекулами, которые регулируют инфекцию. Кроме того, мы обсуждаем важнейший вклад исследований аденовирусного генного экспрессии в выяснение фундаментальных

Совпадение в аннотации оригинала
Animal viruses are well recognized for their ability to uncover fundamental cell and molecular processes, and adenovirus certainly provides … d viral small RNAs. As a nonenveloped virus, adenoviruses have furnished insights into the modes of virus attachment, entry, and penetration of host cells, and we discuss the diversity of cell receptors that support these processes, as well as membrane penetration. As a result of these extensive studies, adenovirus vectors were among the first to be developed for …

Bridging the past and the future of virology: surface plasmon resonance as a powerful tool to investigate virus/host interactions.

Despite decades of antiviral drug research and development, viruses still remain a top global healthcare problem. Compared to eukaryotic cells, viruses are composed by a limited numbers of proteins that, nevertheless, set up multiple interactions with cellular components, allowing the virus to take control of the infected cell. Each virus/host interaction can be considered as a therapeutical target for new antiviral drugs but, unfortunately, the systematic study of a so huge number of interactions is time-consuming and expensive, calling for models overcoming these drawbacks. Surface plasmon r

Co-expression of sialic acid receptors compatible with avian and human influenza virus binding in emus (Dromaius novaehollandiae).

Influenza A viruses (IAVs) continue to threaten animal and human health with constant emergence of novel variants. While aquatic birds are a major reservoir of most IAVs, the role of other terrestrial birds in the evolution of IAVs is becoming increasingly evident. Since 2006, several reports of IAV isolations from emus have surfaced and avian influenza infection of emus can lead to the selection of mammalian like PB2-E627K and PB2-D701N mutants. However, the potential of emus to be co-infected with avian and mammalian IAVs is not yet understood. As a first step, we investigated sialic acid (S

Poliovirus and its cellular receptor: a molecular genetic dissection of a virus/receptor affinity interaction.

The ability of a virus to attach to a susceptible host cell is of utmost importance for the initiation of viral life cycle. Cell surface proteins called viral receptors mediate the initial steps of virus attachment and uptake. Poliovirus (PV) is one of the most studied animal viruses and its interaction with its cellular receptor, the human poliovirus receptor (hPVR) has been well characterized. This review will present our current understanding of the PV/hPVR interaction at the genetic and biochemical level. In addition, we will also discuss the implications of the PV/hPVR interaction on PV t…

Broad neutralization of CSFV with novel monoclonal antibodies in vivo.

Classical swine fever is a highly contagious disease in China. Although vaccination against Classical swine fever virus (CSFV) has been widely carried out in China, CSFV cases still emerge in an endless stream. Therefore, it is necessary to take new antiviral measures to eliminate CSFV. Glycoprotein E2 of CSFV is the major vaccine candidate that confers protective immunity. Thus, in this study, a batch of neutralizing monoclonal antibodies (mAbs) against E2, as alternative antiviral strategies, were produced. Among them, mAbs 6D10, 8D8 and 3C12 presented neutralizing reactivity against CSFV in

Role of sulfatide in vaccinia virus infection.

BACKGROUND INFORMATION: Vaccinia virus (VACV) was used as a surrogate of variola virus (genus Orthopoxvirus), the causative agent of smallpox, to study orthopoxvirus infection. VACV infects cells via attachment and fusion of the viral membrane with the host cell membrane. Glycosphingolipids, expressed in multiple organs, are major components of lipid rafts and have been associated with the infectious route of several pathogens. RESULTS: We demonstrate that the VACV-WR (VACV Western-Reserve strain) displays no binding to Cer (ceramide) or to Gal-Cer (galactosylceramide), but binds to a natural

Polymer-bound 6' sialyl-N-acetyllactosamine protects mice infected by influenza virus.

To develop a mouse model for testing receptor attachment inhibitors of human influenza viruses, the human clinical virus isolate in MDCK cells A/NIB/23/89M (H1N1) was adapted to mice by serial passaging through mouse lungs. The adaptation enhanced the viral pathogenicity for mice, but preserved the virus receptor binding phenotype, preferential binding to 2-6-linked sialic acid receptors and low affinity for 2-3-linked receptors. Sequencing of the HA gene of the mouse-adapted virus A/NIB/23/89-MA revealed a loss of the glycosylation sites in positions 94 and 163 of HA1 and substitutions 275Asp

A Haploid Genetic Screen Identifies Heparan Sulfate Proteoglycans Supporting Rift Valley Fever Virus Infection.

UNLABELLED: Rift Valley fever virus (RVFV) causes recurrent insect-borne epizootics throughout the African continent, and infection of humans can lead to a lethal hemorrhagic fever syndrome. Deep mutagenesis of haploid human cells was used to identify host factors required for RVFV infection. This screen identified a suite of enzymes involved in glycosaminoglycan (GAG) biogenesis and transport, including several components of the cis-oligomeric Golgi (COG) complex, one of the central components of Golgi complex trafficking. In addition, disruption of PTAR1 led to RVFV resistance as well as red

Ocular infection of mice with influenza A (H7) viruses: a site of primary replication and spread to the respiratory tract.

Avian H7 influenza viruses have been responsible for poultry outbreaks worldwide and have resulted in numerous cases of human infection in r … d primary human corneal epithelial cells (in vitro). Influenza viruses were labeled to identify the virus attachment site in the mouse cornea. Although we found abundant H7 virus attachment to corneal epithelial tissue, this did not account for the differences in virus replication as multiple subtypes were able to attach to these cells. These findings demonstrate …

Discovery of acridone analogs as novel entry inhibitors targeting e protein of dengue virus.

The envelope (E) protein of the Dengue virus (DENV) is critical for virion attachment and membrane fusion with the host cell, as well as the release of the viral RNA genome into the cytoplasm. In this study, we describe the design, synthesis, and biological evaluation of novel viral entry inhibitors containing an acridone core. Notably, compound 13e demonstrated potent cellular antiviral activity (IC50 = 8.6 μM and selectivity index = 21.4). Compound 13e was evaluated using several methods, including time-of-addition and virus entry/binding assays, which revealed that it selectively blocked DE

Nanoscopy reveals heparan sulfate clusters as docking sites for SARS-CoV-2 attachment and entry.

Virus entry is thought to involve binding a unique receptor for cell attachment and cytosolic entry. For SARS-CoV-2 underlying the COVID-19 pandemic, angiotensin-converting enzyme 2 (ACE2) is widely considered the receptor for cell-surface attachment and subsequent cell entry. Using advanced light microscopy to resolve individual virions and receptors, we found instead that heparan sulfate (HS), not ACE2, mediates SARS-CoV-2 cell-surface attachment, and subsequent endocytosis. ACE2 functions only downstream of HS to enable viral genome expression. Instead of binding single HS molecules that el

Гепаратная сульфатная связь с вирусом инфекционного денге типа 2 и вирусом желтой лихорадки.

Вирус денге типа 2 и вирус Желтой лихорадки - это артропроподовые ароматизаторы, вызывающие геморрагическую лихорадку у людей. Идентификация вирусных рецепторов имеет важное значение для понимания патогенеза флавивируса. Цель этой работы заключалась в изучении роли сульфата клеточной гепары в адсорбции инфекционных желтых лихорадок и вирусов денге типа 2. Вирусное соединение оценивалось путем адсорбирования вируса к клеткам, стирания незамысловатого вируса, высвобождения вируса привязки к клеткам путем замерзания/отталкивания, а затем заклеивания высвобожденного инфекционного вируса. Лечение к

Совпадение в аннотации оригинала
Dengue virus type 2 and Yellow fever virus are arthropod-borne flaviviruses causing hemorrhagic fever in humans. Identification of virus rec … of cellular heparan sulfate in the adsorption of infectious Yellow fever and Dengue type 2 viruses. Virus attachment was assessed by adsorbing virus to cells, washing unbound virus away, releasing cell-bound virus by freezing/thawing, and then titrating the released infectious virus. Treatment of cells by heparin-lyase, desulfation of cellular heparan sulfate, or …

Flavivirus entry into cultured mosquito cells and human peripheral blood monocytes.

The entry modes of Japanese encephalitis (JE) and dengue-2 (DEN-2) viruses into C6/36 mosquito cells and of DEN-2 virus into human peripheral blood monocytes in vitro were studied. Inoculation of either JE or DEN-2 virions into C6/36 cells resulted in direct penetration of the virions into the cytoplasm at the cell surface in 3 stages. At stage 1, virions attached to the plasma membrane of host cells by their envelope spikes; at stage 2, the virion envelopes approximated to and eventually overlapped the host plasma membrane, and in the process the plasma membrane at the attachment sites dissol

Emulsifiers that enhance susceptibility to virus infection: increased virus penetration and reduced interferon response.

An emulsifier which had an environmental relationship to Reye's syndrome, when used to treated L-929 cultures, was shown to increase the rate of encephalomyocarditis virus penetration and uncoating while having no effect on the attachment of virus or on the replication of infectious ribonucleic acid. This treatment also rendered L-929 cells unable to respond normally to interferon inducers and reversed an already established interferon antiviral state. It is proposed that one or more of these actions result in the cellular enhancement of virus susceptibility.

The role of DC-SIGN and DC-SIGNR in HIV and Ebola virus infection: can potential therapeutics block virus transmission and dissemination?

Sexual transmission of HIV requires that the virus crosses mucosal barriers and disseminates into lymphoid tissue, the major site of viral replication. To achieve this, HIV might engage DC-SIGN, a calcium dependent lectin that is expressed on mucosal dendritic cells (DCs), which binds avidly to HIV. DC-SIGN and other attachment factors are likely to account for the well-known ability of DCs to enhance infection of T cells by HIV. Attachment of HIV to DC-SIGN might thus enhance viral spread in mucosal tissues and, by taking advantage of the inherent capacity of DCs to migrate into lymphoid tiss