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At least 19 recordsLinked to original sources
PubMed1978

[Increase in the antiviral resistance of cells after treating them with messenger RNA for antiviral protein].

The authors studied antiviral resistance of murine cells L-929 following single introduction into them of homologous and heterologous informative RNA preparations for antiviral protein (i-RNA-AVP). As shown, in using homologous i-RVA-AVP preparations suppression of the virus production constituted 90--93%, and was stably traced in cell passage in the course of 1 1/2 months (observation period). Following cell contact with heterologous i-RNA-AVP preparations suppression the first 6 passages of the virus production constituted about 90%, rising by the 16th passage to 99.9%. The data obtained pointed to the possibility of stable increase of cell antiviral resistance with the aid of i-RNA-AVP, this could serve as a new effective method of nonspecific cell protection from the viruses.

Animals↗
PubMed2025

Intracellular interactions shape antiviral resistance outcomes in poliovirus via eco-evolutionary feedback.

Antiviral resistance evolution poses a major obstacle for controlling viral infections. A promising strategy is to target shared viral proteins that allow drug susceptible viruses to sensitize resistant ones during cellular coinfection, muting selection for resistance. Pocapavir, a poliovirus capsid inhibitor, employs this sociovirological strategy. While susceptible viruses significantly suppressed resistance in the presence of pocapavir in cell culture, a pocapavir clinical trial observed widespread resistance evolution and limited improvements to clearance times. To reconcile these findings, we present an intra-host eco-evolutionary model of poliovirus in the presence of pocapavir, which reproduces both the potent interference observed in vitro and the resistance emergence seen in patients. In the short term, our model predicts that a high density of susceptible viruses sensitizes resistant ones to pocapavir, mirroring cell culture results. However, over multiple replication cycles, pocapavir's high potency collapses viral density, which reduces coinfection and allows resistance to evolve as observed in the clinical trial. Since coinfection is essential to suppress resistance, enabling greater survival of susceptible viruses could offer therapeutic advantages. Counterintuitively, we demonstrate that this can be achieved by lessening antiviral potency, which can limit resistance evolution while also maintaining a low viral load. These findings suggest that antivirals that rely on viral intracellular interaction must balance immediate neutralization with the preservation of future coinfection, yielding more sustained inhibition. Explicitly considering the eco-evolutionary feedback encompassing viral density, shared phenotypes and absolute fitness not only provides new insights into designing effective therapies but also illuminates viral evolutionary dynamics more broadly.

Journal Article↗
PubMed2026

Detection and characterization of antiviral-resistant viruses during the influenza season of 2024-25.

UNLABELLED: During the high severity season of 2024-25, CDC with public health partners sequenced and analyzed genomes of >10,000 influenza viruses for antiviral resistance markers. Available sequence-flagged and representative viruses were tested with antivirals using in vitro assays. In the US, three oseltamivir-resistant A(H3N2) viruses had treatment-emergent neuraminidase (NA) mutations, either E119V or R292K. Oseltamivir-resistant A(H1N1)pdm09 viruses with NA-H275Y were detected in 15 states, albeit at a low frequency (0.53%). They belonged to several phylogenetic groups, with hemagglutinin (HA) subclade D.3.1 combined with either NA subclade D.1 or D.2 being most common. Based on shared sequence data, nearly all H275Y viruses from Australia, Canada, and Chile also belonged to these HA and NA subclades. Conversely, most H275Y viruses (68/81) from China belonged to HA subclade C.1.9 and NA subclade D and shared the permissive mutation R257K. Influenza polymerase acidic (PA) mutations conferring 4- to 92-fold decreased baloxavir susceptibility were detected in nine influenza A viruses. Viruses with PA-I38T showed mild attenuation of replicative fitness in three cell lines. Based on available data, NA-H275Y and PA-I38T viruses were collected from patients with no exposure to antivirals. Baseline susceptibility to all US-approved influenza antivirals remained largely unchanged compared to previous seasons. All swine-origin viruses detected in the US had adamantane resistance-conferring marker, M2-S31N, but remained susceptible to other approved antivirals. Monitoring antiviral susceptibility has substantially improved with increased sequencing capacities and bioinformatic support at public health laboratories. Information gained through influenza surveillance has been used to guide recommendations on antiviral use. IMPORTANCE: Circulation of influenza viruses with reduced susceptibility to antivirals can diminish the usefulness of medications prescribed for influenza. This study informs on the prevalence of drug-resistant influenza viruses in the US during the high severity season of 2024-25. It provides information on susceptibility profile to all approved antiviral medications and on replicative fitness of representative drug-resistant viruses. Most drug-resistant viruses were collected from patients who were not exposed to antivirals indicating their ability to transmit from human to human. Whole-genome sequence (WGS)-based analysis is the cornerstone for surveillance, and numerous laboratories have been utilizing this approach. However, CDC laboratory is the only laboratory in the US conducting phenotypic testing of circulating viruses needed to confirm the outcomes of sequence-based analysis and to identify new molecular markers of resistance. Data gathered through virologic surveillance give much-needed information on drug susceptibility of influenza viruses which are used to guide recommendations on antiviral use.

Antiviral Agents↗
PubMed1977

Effect of impulsin treatment of interferon production and antiviral resistance of mice.

The effect of N-(2-hydroxyethyl)-palmitamide (Impulsin, Spofa)--an active endogenous compound which is recommended for preventing virus infection of the respiratory tract--on interferon production in mice stimulated with double stranded RNA and on the course of disease caused by encephalomyocarditis virus (EMC) was studied. Impulsin itself did not stimulate interferon production in mice treated per os or intravenously. But repeated application of this drug per os induced a macrophage activation, reflected by enhanced interferon production in vitro. When the interferon stimulation was delayed until 4 to 10 days after the first dose of Impulsin, interferon response to ds-RNA was slightly increased. After this phase of enhanced activity a decreased production of interferon was observed. Impulsin was not significantly effective in protecting mice from lethal dose of EMC virus. Application of this drug had an inhibitory effect on the toxicity of ds-RNA. A possible explanation of the mechanism by which Impulsin decreased the toxicity of virus in the organism is discussed.

Animals↗
PubMed1977

The transfer of interferon-induced viral resistance between animal cells.

In summary we have shown that interferon treated mouse L cells can transfer their antiviral resistance to cocultured heterologous (human WISH or hamster BHK) cells which are insensitive to mouse interferon. Transfer of viral resistance seems to be initiated by interferon itself. Once transferred the viral resistance has the characteristics of the interferon-induced antiviral state. The transferred resistance occurs between several cell species. The transfer of resistance depends on the ratio of cells homologous (to interferon) to cells which are heterologous as well as to the absolute cell density at a given ratio. The transfer process is efficient in that it requires relatively small amounts of interferon. Finally, we propose that this phenomenon is a natural process for amplification of the interferon system and preliminary evidence indicates that it occurs by cell to cell transfer of an interferon-induced molecule.

Animals↗
PubMed2026

A conserved COBL3-like protein promotes PDLP5-dependent callose accumulation to confer broad-spectrum plasmodesmata-mediated antiviral defense.

Plasmodesmata (PDs) play vital roles in plant growth and defense by controlling the symplastic transport of important molecules. Here we report that a conserved COBRA-like protein, COBL3, positively regulates callose accumulation and is required for PD-mediated antiviral defense (PMAD) against divergent plant RNA viruses in wheat (Triticum aestivum) and tobacco (Nicotiana benthamiana). The wheat COBL3 protein, TaCOBL3, interacts with the 17K movement protein (MP) of barley yellow dwarf virus-GAV (BYDV-GAV). TaCOBL3 is associated with the plasma membrane and co-localizes with 17K MP at PDs. Genetic analysis with overexpression and knockout lines revealed that TaCOBL3 positively regulates wheat defense against BYDV-GAV by modulating callose accumulation at PDs. Interestingly, TaCOBL3 interacts with the wheat homolog of PDLP5, a conserved key regulator of PD permeability in higher plants. Silencing TaPDLP5 attenuates the elevated BYDV-GAV defense conferred by overexpression of TaCOBL3 in wheat. Furthermore, transient expression of TaCOBL3 promotes callose accumulation and lowers PD permeability in tobacco cells, and these effects are largely compromised when tobacco PDLP5 is silenced. Notably, BYDV 17K MP weakens the interaction between TaCOBL3 and TaPDLP5 and inhibits their callose-binding activities. Finally, silencing of tobacco NbCOBL3 reduces callose content and attenuates host defense against two tobraviruses, one potexvirus, and one hordeivirus. Overall, our study reveals a previously unknown role of COBRA-like proteins in PMAD and provides insight into how a plant viral MP sabotages PMAD by perturbing the COBL3-PDLP5 interaction to facilitate virus spread through PDs. The conserved COBL3 gene may be a valuable target for engineering of broad-spectrum antiviral resistance in crop plants.

COBRA-like protein↗
PubMed1979

Macrophage immunity to influenza virus: in vitro and in vivo studies.

Using M-TUR, a macrophage-adapted avian influenza A virus (Hav1, Nav3), antiviral resistance of peritoneal macrophages obtained from specifically or nonspecifically immunized mice towards in vitro infection was assessed. M-TUR grew to high titers in macrophages from nonimmune mice thereby causing a marked cytopathic effect. In contrast, peritoneal macrophages from mice specifically immunized with TUR virus were not affected by infection with M-TUR in vitro. This antiviral immunity was specific: mice immunized with antigenetically unrelated influenza strains such as influenza A/Hong Kong/1/68 (H3, N2) or influenza B/Lee yielded susceptible macrophages. Specific macrophage immunity could be abrogated by trypsin treatment in vitro. Susceptible macrophages from nonimmune hosts became resistant following in vitro exposure to homologous anti-TUR sera. Peritoneal exudate cells from BCG-infected animals were less susceptible to in vitro challenge with M-TUR than control macrophages. In vivo treatment of mice with the unspecific immunostimulants BCG or Corynebacterium parvum did not protect the animals against lethal infection with a hepatotropic variant of TUR.

Animals↗
PubMed1979

Route of infection, systemic host resistance, and integrity of ganglionic axons influence acute and latent herpes simplex virus infection of the superior cervical ganglion.

The character of acute and latent herpes simplex virus (HSV) infection of the superior cervical ganglion (SCG) in mice depended on the route by which the virus reached the ganglion, the level of systemic host resistance, and the integrity of postganglionic nerves. Prevention of ganglionic infection by postganglionic neurectomy carried out before intraocular (i.o.) virus challenge established the importance of the neural route in the development of SCG infection. However, hematogenous virus dissemination also led to SCG infection although with reduced frequency compared to that with i.o. inoculation. Enhanced host systemic antiviral resistance had two divergent effects on ganglionic infection depending on the dose and timing of virus inoculation. Thus, both acute and latent ganglionic infections were concomitantly reduced when resistant C57B1/6 mice were challenged with low doses of virus or when less resistant BALB/c mice were actively immunized 1 week before virus challenge. On the other hand, when resistant mice were challenged with high doses of virus or when either active or passive (antibody) immunization was delayed long enough to assure viral access to the ganglion, intraganglionic viral replication during the acute phase of infection was reduced, but the prevalence of subsequent latent infection was either unaffected or actually enhanced. Postganglionic neurectomy, performed after virus had reached the ganglion, altered the course of SCG infection in a direction opposite that of immunization, augmenting the acute phase of viral replication while reducing latency. In athymic nude mice and mice immunosuppressed with cyclophosphamide, intraganglionic viral replication was prolonged. These results emphasize that host factors both extrinsic and intrinsic to the SCG modify the course of ganglionic infection.

Acute Disease↗
PubMed1979

[Effect of a natural interferon inducer (RFf2) on the formation of vaccinal immunity to tick-borne encephalitis].

The effect of the interferon inductor of the natural origin (RFf2) on formation of vaccinal immunity to vernal encephalitis was studied. A single intraperitoneal administration of the preparation in a dose of 10 gamma per a mouse 2 hours after the first injection of the vaccine resulted in increased resistance of the mice to the lethal dose of the infecting virus which was introduced 14 days after the vaccination completion. The production dynamics of interferon induced by RFf2 and its level in the serum of the immunized mice were the same as those in the non-vaccinated animals. An increased number of the vaccine injections, up to 3 did not result in a significant increase in the immunity with respect to either the level of the antiviral resistance or the level of the virus-neutralizing antibody accumulation.

Animals↗
PubMed1977

[Potentiating effect of cycloheximide on viral interference].

The degradation of the antiviral state can be delayed in vitro by antimetabolites, when added between 5-7 hours after interferon. We explore in this chronological order whether antiviral resistance induced by Newcastle disease virus (N.D.V.) in vivo could be modified by an antimetabolite. Cycloheximide was selected for this study because of its reversible biological effect and lack of toxicity in our experimental conditions. The model system employed was Syrian Hamsters, using N.D.V. as an interferon inducer and encephalomyocarditis virus (E.M.C.) as a challenge virus. A constant and significant increase in survival of animals treated with N.D.V.+cycloheximide is probably related to a delay in the degradation of the antiviral state and not to interferon superinduction.

Animals↗
PubMed2026

A bireporter recombinant SARS-CoV-2 Omicron BA.5 for in vitro and in vivo studies.

The continuous emergence of variants of concern (VoCs) represents a significant challenge to effectively control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although FDA-approved vaccines and antivirals have been successfully developed and implemented for the prophylactic and therapeutic intervention of SARS-CoV-2 infection, recent VoCs could escape protection garnered by previous vaccine and antiviral approaches. Determining the efficacy of prophylactics and/or therapeutics against recent VoCs will assist in efficiently controlling currently circulating SARS-CoV-2 strains. We used our previously described bacterial artificial chromosome-based reverse genetics approach for Omicron BA.5 to generate a recombinant SARS-CoV-2 BA.5 encoding a fusion of ZsGreen to Nanoluciferase (rBA.5 ZsG-Nluc) from the locus of the viral nucleocapsid (N) protein separated by the porcine teschovirus-1 2A proteolytic cleavage site. The rBA.5 ZsG-Nluc replicates to levels comparable to recombinant BA.5 wild type (rBA.5 WT) and expresses high levels of ZsG and Nluc in cultured cells. This facilitates tracking viral infection and the identification of antivirals and neutralizing antibodies with EC50 and NT50 values, respectively, similar to those obtained with rBA.5 WT. Importantly, in Keratin-18 human angiotensin-converting enzyme-2 mice, rBA.5 ZsG-Nluc retains the same pathogenicity and ability to replicate in the lungs of infected mice as rBA.5 WT. Using rBA.5 ZsG-Nluc, we detected Nluc activity systemically and Nluc and ZsG expression in the lungs of infected mice using an in vivo imaging system. Our results demonstrate the feasibility of using rBA.5 ZsG-Nluc to track viral infections and identify prophylactics and therapeutics against recent SARS-CoV-2 VoCs in vitro, ex vivo, and in vivo.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of the coronavirus disease 2019 pandemic, is continually evolving to escape immunity acquired by previous natural infections or vaccinations. Moreover, recent SARS-CoV-2 variants of concern (VoCs) have acquired antiviral-resistant mutations to FDA-approved drugs. The emergence of these VoCs highlights the importance of identifying new prophylactics and therapeutics against currently circulating SARS-CoV-2 strains. We generated a recombinant bireporter Omicron BA.5 SARS-CoV-2 (rBA.5 ZsG-Nluc) that expresses reporter proteins, which are useful for cellular and whole animal studies, and has similar viral replication and pathogenicity to a wild-type recombinant Omicron BA.5 SARS-CoV-2. In Keratin-18 human angiotensin-converting enzyme-2 mice, rBA.5 ZsG-Nluc infection can be tracked systemically or in the lungs of infected mice using an in vivo imaging system. We establish a proof-of-concept platform of rBA.5 ZsG-Nluc in combination with an ancestral SARS-CoV-2 strain expressing mCherry to simultaneously identify antivirals and neutralizing antibodies against original and recent SARS-CoV-2 strains.

SARS-CoV-2↗
PubMed1979

Potentiation of interferon activity by mixed preparations of fibroblast and immune interferon.

Mixed preparations of fibroblast and immune interferons interacted with cells synergistically to cause the development of a much greater level of protection than expected on the basis of their separate activities. This increased level of protection was 5- to 20-fold greater than expected on the basis of a simple additive effect of the interferons. The potentiating factor copurified with both fibroblast interferon and immune interferon as they were partially purified. The potentiation was not an artifact of a more rapid development of immune interferon-induced antiviral resistance in the presence of fibroblast interferon. The results were consistent with the hypothesis that fibroblast and immune interferons mutually potentiate each other, thus supporting the supposition that they have different modes of action.

Animals↗
PubMed2026

Complete Genome Sequencing of Occult Hepatitis B Virus in Hemodialysis Patients Reveals Subgenotype D2 and Immune Escape Mutations in Bangladesh.

Hepatitis B virus (HBV) remains a major global health concern, and occult HBV infection (OBI) presents significant diagnostic and clinical challenges, particularly among hemodialysis (HD) patients. This study is aimed at characterizing complete HBV genomes from maintenance HD patients with OBI in Bangladesh to elucidate genetic features, mutational patterns, and clinical implications. Serum samples from two HBsAg-negative HD patients were screened by ELISA and quantitative PCR. Viral DNA was amplified by PCR across four overlapping open reading frames (ORFs) and sequenced on the Illumina platform. Genome assembly, phylogenetic analysis, and mutational profiling were performed using reference datasets and bioinformatics tools. Antigenicity and hydrophilicity of HBsAg were predicted in silico. Both patients were anti-HBc and anti-HBs positive with high HBV DNA loads (2.29 × 1010 and 2.53 × 1010 copies/mL). Full-length genomes (3182 bp) were successfully sequenced and phylogenetic analysis showed both HBV genomes clustered within Genotype D, Subgenotype D2, and subtype ayw3, consistent with previously reported Bangladeshi HBV genomes. Comparative mutational analysis identified substitutions such as T1753C in the basal core promoter, C1845T in preC, and D144E within the "a" determinant of HBsAg, suggesting potential roles in vaccine escape, immune escape, and diagnostic failure. Several nonsynonymous mutations were also detected in polymerase, though none were potentially associated with antiviral resistance. Antigenicity and hydrophilicity profiles of HBsAg and its major hydrophilic region remained largely conserved. These findings demonstrate the persistence of OBI in HD patients and provide an initial indication of the need for genomic surveillance to monitor immune-escape mutations and improve HBV diagnostic strategies in endemic regions.

HBV genome sequencing↗
PubMed1977

Influenza virus antigens in human leukocytes after oral administration of live tissue culture influenza A monovaccine.

Influenza A virus antigens were detected in leukocytes by immunofluorescence. After intravenous inoculation of the A/Moscow/16/65 (H2N2) vaccine strain to chickens, cytoplasmic antigens of the virus were observed in mononuclear leukocytes from 24 to 72 hours post inoculation (p.i.). The course of antigen detectability was similar after two repeated inoculations of the virus. After oral vaccination of human volunteers with a live tissue culture influenza A monovaccine from the X-47 (H3N2) recombinant viral antigens were also found in mononuclears; the maximal number of antigen-positive cells was observed at 24 hours p.i. The method of membrane immunofluorescence proved to be the most sensitive for antigen detection; it revealed a considerable decrease in the number of antigen-positive cells after repeated administration of the virus to volunteers. This fact may possibly reflect the development of antiviral resistance in the process of vaccination.

Administration, Oral↗
PubMedDate not supplied

[Cellular mediated immunity in virus infections].

The intervention of cellular immunity in the course of specific antiviral defence is suggested or confirmed by a series of clinical and experimental findings, i.e. the evolution of certain viral diseases following a second contact with viral antigens; discrepancy between the level of antiviral serum antibodies and the clinical course of some viral diseases; pathohistological alterations in some viral diseases, suggesting the intervention of cellular immunity; the clinical aspects of natural or experimental viral diseases in primary and secondary immunodeficiency. Investigations were likewise carried out on certain indices of cellular immunity in human or experimental viral diseases, such as delayed hypersensitivity skin tests; the transfer of immune lymphocytes; lymphocytic blastic transformation; inhibition of macrophage migration; specific cytotoxicity test. The problems concerning the role of cellular immunity in the specific defence against viruses may be grouped as follows: mechanisms of induction of the immune cellular response in viral infections; relationship between cellular and humoral immunity in antiviral resistance; relative independance of systemic and local cellular immunity in the course of viral diseases; the cellular basis of cellular mediated immunity in viral diseases.

Animals↗
PubMed1979

Attempt to transfer priming by cocultivation of L cells and chick embryo fibroblasts.

Interferon-treated L cells did not transfer priming to chick embryo fibroblasts (CEF) during cocultivation. Nor could transfer be observed when CEF were treated with homologous interferon in the mixed cultures. The results indicate that the lack of transfer by cocultivation is another characteristic of priming different from antiviral resistance.

Animals↗