Inhibition Of Viral Activity Research Articles

Synthesis of camphecene derivatives using click chemistry methodology and study of their antiviral activity

A series of seventeen tetrazole derivatives of 1,7,7-trimethyl-[2.2.1]bicycloheptane were synthesized using click chemistry methodology and characterized by spectral data. Studies of cytotoxicity and in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells of the compounds obtained were performed. The structure-activity relationship analysis suggests that to possess virus-inhibiting activity, the compounds of this group should bear oxygen atom with a short linker (C2-C4), either as a hydroxyl group (18, 19, 29), keto-group (21) or as a part of a heterocycle (24). These compounds demonstrated low cytotoxicity along with high anti-viral activity.

Ethanol extract and chromatographic fractions of Tamarindus indica stem bark inhibits Newcastle disease virus replication

Context: The plethora of ethnomedicinal applications of Tamarindus indica Linn. (Leguminosae), tamarind, includes treatment of human and livestock ailments; preparations are recognized antipyretics in fevers, laxatives and carminatives. African folklore has various applications of tamarind. However, in Nyasaland, domestic fowl are fed with preparations for prophylactic properties.Objectives: The objective of this study is to evaluate the antiviral properties of T. indica extract.Materials and methods: Tamarindus indica stem bark was extracted through ethanol maceration over 24 h, and the crude extract was fractionated by gravity-propelled column chromatography. Newcastle disease virus (NDV) inhibitory activity of extract and fractions were evaluated in vivo using 10-d-old embryonated chicken egg (ECE) as the medium for virus cultivation and antivirus assay. About 240 ECE were grouped into eight (three controls and five experimental) and, 200 μL of the extract and fractions respectively inoculated into NDV pre-infected eggs and incubated at 37 °C. Allantoic fluid was harvested 5 d post-virus infection and assayed for haemagglutination (HA).Results: Anti-NDV assessment showed 62.5 mg/mL of crude extract and fractions: TiA, TiC and TiD to yield a HA titre of 1:128 each, while TiB showed 1:64 HA titre. At 125 mg/mL, a titre of 1:16 was recorded against TiB and TiD and, 1:8 against TiA. Similarly, crude extract and TiC, each recorded 1:4 HA titre. However, the minimum concentrations of extract and fraction for virus inactivation were 0.24 mg/mL and 0.49 mg/mL, respectively.Conclusion: The antiviral activity shown by T. indica portends novel antiviral drugs and, perhaps, as scaffold for new drugs.

Tautomeric and non-tautomeric N-substituted 2-iminobenzimidazolines as new lead compounds for the design of anti-influenza drugs: An in vitro study

A series of 1,3-disubstituted 2-iminobenzimidazolines as well as a number of their tautomeric analogs were synthesized. The synthesized compounds were tested for their cytotoxicity against MDCK cells and for inhibiting activity against influenza virus A/California/07/09 (H1N1)pdm09. Based on the results obtained, 50% cytotoxic concentration (CC50), 50% inhibiting concentration (IC50) and selectivity index (SI) were calculated for each compound. It was found that some of synthesized benzimidazole derivatives (7 of 22, 32%) possess strong virus-inhibiting activity against pandemic influenza virus (IC50’s in low micromolar range) with quite moderate cytotoxicity (CC50 in the range of thousands micromoles). Due to their high selectivity (highest SI’s=50–83) these compounds are of significant interest for further in vivo experiments as well as for further structural optimization and drug development.

Virus-inhibiting activity of dihydroquercetin, a flavonoid from Larix sibirica, against coxsackievirus B4 in a model of viral pancreatitis.

Members of the family Picornaviridae, in particular, enteroviruses, represent a serious threat to human health. They are responsible for numerous pathologies ranging from mild disease to fatal outcome. Due to the limited number of safe and effective antivirals against enteroviruses, there is a need for search and development of novel drugs with various mechanisms of activity against enteroviruses-induced pathologies. We studied the effect of dihydroquercetin (DHQ), a flavonoid from larch wood, on the course of pancreatitis of white mice caused by coxsackievirus B4 (CVB4). DHQ was applied intraperitoneally at doses of 75 or 150mg/kg/day once a day for 5days postinfection (p.i.) starting on day 1p.i., and its effect was compared to that of the reference compound ribavirin. The application of DHQ resulted in a dose-dependent decrease in the virus titer in pancreatic tissue, reaching, at the highest dose, 2.4 logs on day 5p.i. Also, the application of DHQ led to restoration of antioxidant activity of pancreatic tissue that was impaired in the course of pancreatitis. Morphologically, pancreatic tissue of DHQ-treated animals demonstrated less infiltration with inflammatory cells and no signs of tissue destruction compared to placebo-treated mice. Both ribavirin- and DHQ-treated animals developed fewer foci of pancreatic inflammation per mouse, and these foci contained fewer infiltrating cells than those in placebo-treated mice. The effect of DHQ was comparable to or exceeded that of ribavirin. Taken together, our results suggest high antiviral activity of DHQ and its promising potential in complex treatment of viral pancreatitis.

Prevention of Adenovirus Infection with Recombinant Interferon 2b Medication in Preschool Institutions

This article presents the results of experimental (on cell cultures) and clinical (in children’s groups) studies of recombinant interferon alpha-2b medication (Grippferon). Our aim was to examine the virus-inhibitory activity of this medication (against adenovirus) and its preventive effect (on causative agents of ARVI), which allows us to use this medication as a preventive measure against adenovirus (as well as any other) infection in children’s groups.

Virus inhibitory activity of methanol extracts of Halimodendron halodendron Voss.

Virus inhibitory activity of methanol extracts of Halimodendron halodendron Voss.

P15.03 Development of a new cem reporter t-cells (gxr-cells) viral inhibition assay (via) for elucidating the role of class-i-hla alleles on the inhibitory capacity of hiv-1-specific cd8+t-cells

Introduction Standard immunogenicity assays, such as ELISpot and intracellular cytokine staining, fail to correlate HIV-1-specific CD8 + T-cells responses with HIV-1 replication in-vivo . Therefore, it is essential to develop assays that can determine antiviral potential of vaccine elicited CD8 + T-cells. The current ELISA-VIA measures HIV-1-p24 production overtime in autologous CD4 + T-cells. However, it is not designed to identify the class-I-HLA-allele involved in mediating the response. We developed a new FACS based VIA that can investigate CD8 + T-cells antiviral potential in the context of restricting class-I-HLA alleles. The assay measures the ability of CD8 + T-cells to kill HIV-1 infected GXR-cells over-expressing class-I-HLA allele of interest. The assay utilises a GXR-cell engineered to express GFP upon HIV-1 infection. Methods CD8 + T-cells were co-cultured with HIV-1 infected GXR-cells for 3 days. Reduction in the infected GXR-cells expressing GFP measured by FACS was used to evaluate the CD8 + T-cells killing activity. The assay was validated using a panel of 9 HIV-infected samples and were concurrently assayed with the ELISA-VIA. The tested results on each assay were categorised into four groups namely: true-inhibition (TI ≥50%), doubtful-inhibition (DI ≥20% to ≤49.99%), false-inhibition (FI ≥10% to ≤19.99%) and non-inhibition (NI≤ 9.99%). These results were used in a 2 by 2 table to compute sensitivity (TI/TI+DI) and specificity (FI/FI+NI). Results True inhibition was observed in 44% of samples analysed using GXR-VIA compared to 33% with ELISA-VIA. 11% with GXR-VIA had doubtful result compared to 33% with ELISA-VIA. 22% with GXR-VIA were categorised as false inhibition compared to 33% with ELISA-VIA. Interestingly, no sample showed non-inhibition with GXR-VIA whereas 22% showed no inhibition by ELISA-VIA. Collectively, GXR-VIA is very specific (100%) but less sensitive (57%) at detecting virus inhibition activity. Conclusion The specificity of GXR-VIA and its marginal sensitivity indicates that the assay is capable of identifying CD8 + T-cells-mediated inhibition of HIV-1 replication. Overall, the GXR-VIA provides a platform to assess the influence of different restricting class-I-HLA alleles on HIV-1-specific CD8 + T-cells antiviral function.

Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8(+) T-cell responses and disease progression.

The aim of this study was to analyze Th17 and Treg subsets and their correlation with anti-HIV T-cell responses and clinical parameters during (acute/early) primary HIV infection (PHI) and up to one year post-infection (p.i). Samples from 14 healthy donors (HDs), 40 PHI patients, 17 Chronics, and 13 Elite controllers (ECs) were studied. The percentages of Th17 and Treg subsets were severely altered in Chronics, whereas all HIV-infected individuals (including ECs) showed Th17/Treg imbalance compared to HDs, in concordance with higher frequencies of activated CD8+ T-cells (HLA-DR+/CD38+). Better clinical status (higher CD4 counts, lower viral loads and activation) was associated with higher Th17 and lower Treg levels. We found positive correlations between Th17 at baseline and anti-HIV CD8+ T-cell functionality: viral inhibitory activity (VIA) and key polyfunctions (IFN-γ+/CD107A/B+) at both early and later times p.i, highlighting the prognostic value of Th17 cells to preserve an effective HIV T-cell immunity. Th17/Treg ratio and the IL-17 relative mean fluorescence intensity (rMFI of IL-17) were also positively correlated with VIA. Taken together, our results suggested a potential link between Th17 and Th17/Treg ratio with key HIV-specific CD8+ T-cell responses against the infection.

Anti-chikungunya activity of luteolin and apigenin rich fraction from Cynodon dactylon.

To obtain luteolin and apigenin rich fraction from the ethanolic extract of Cynodon dactylon (L.) (C. dactylon) Pers and evaluate the fraction's cytotoxicity and anti-Chikungunya potential using Vero cells. The ethanolic extract of C. dactylon was subjected to silica gel column chromatography to obtain anti-chikungunya virus (CHIKV) fraction. Reverse phase-HPLC and GC-MS studies were carried out to identify the major phytochemicals in the fraction using phytochemical standards. Cytotoxicity and the potential of the fraction against CHIKV were evaluated in vitro using Vero cells. Reduction in viral replication was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) after treating the viral infected Vero cells with the fraction. Reverse Phase-HPLC and GC-MS studies confirmed the presence of flavonoids, luteolin and apigenin as major phytochemicals in the anti-CHIKV ethanolic fraction of C. dactylon. The fraction was found to exhibit potent viral inhibitory activity (about 98%) at the concentration of 50 µg/mL as observed by reduction in cytopathic effect, and the cytotoxic concentration of the fraction was found to be 250 µg/mL. RT-PCR analyses indicated that the reduction in viral mRNA synthesis in fraction treated infected cells was much higher than the viral infected control cells. Luteolin and apigenin rich ethanolic fraction from C. dactylon can be utilized as a potential therapeutic agent against CHIKV infection as the fraction does not show cytotoxicity while inhibiting the virus.

Three new coumarins from Saposhnikovia divaricata and their porcine epidemic diarrhea virus (PEDV) inhibitory activity

Swine based agro-industries throughout the world are in big threat of new PEDV infection due to lack of efficient prophylactic defenses as well as dependable curing agents. Bioactivity-guided fractionation of a methanol soluble extract from radix of Saposhnikovia divaricata led to the isolation of three new (1–3) together with 10 known coumarins (4–13). The structures of new isolates (1–3) were established by extensive spectroscopic analysis and their absolute configurations were assigned based on ECD spectra calculation and analysis. Among all isolates, compound 5 revealed strongest inhibitory effect on PEDV replication. Quantitative real-time PCR data showed inhibitory effect of 5 on genes responsible for synthesis of PEDV vital structural proteins (GP6 nucleocapsid, GP2 spike, and GP5 membrane) in a dose-dependent manner. Also, compound 5 demonstrated the inhibitory effect on PEDV GP6 nucleocapsid and GP2 spike protein synthesis as analyzed by western blotting. This study represents a new class of chemical entities for developing anti-PEDV agents.

Systemic antiviral resistance induced in papaya by CAP-34, a resistance inducing protein from Clerodendrum aculeatum, is associated with a proteinaceous virus inhibitory activity.

Proteins from non-host higher plants are known to induce systemic resistance in plants against virus infections in susceptible plants. CAP-34 is one such known protein with molecular mass 34 kDa, isolated from Clerodendrum aculeatum. CAP-34 was also shown to be acting against Papaya ringspot virus (PRSV) in papaya by imposing a possible check on PRSV replication. Since the induced resistance was systemic, efforts were made to identify host components that could be involved in it. In the process, a virus inhibitory activity was observed concomitantly with the development of resistance. This paper reports the time- course of the virus inhibitory activity and purification to electrophoretic homogeneity of a proteinaceous virus inhibitory agent (VIA), and the determination of some of its biochemical characteristics. This VIA, denoted CP-VIA-34 based on the host where it came from (Carica papaya), and was determined to be a basic protein that inactivated Tobacco mosaic virus (TMV) ex vivo when bioassayed on Nicotiana tabacum cv Samsun NN. CP-VIA-34 had a molecular mass of 34 kDa, was thermostable and resistant to proteinase K. It did not exhibit protease (tested separately on BSA, and purified TMV), DNase and RNase activities. The paper discusses the characteristics of the CP-VIA-34, and its relevance in relation to some other known plant defence proteins such as the ribosome-inactivating proteins, inhibitor of virus replication, antiviral factor, and the PR-proteins.

Identification of effective subdominant anti-HIV-1 CD8+ T cells within entire post-infection and post-vaccination immune responses.

Defining the components of an HIV immunogen that could induce effective CD8+ T cell responses is critical to vaccine development. We addressed this question by investigating the viral targets of CD8+ T cells that potently inhibit HIV replication in vitro, as this is highly predictive of virus control in vivo. We observed broad and potent ex vivo CD8+ T cell-mediated viral inhibitory activity against a panel of HIV isolates among viremic controllers (VC, viral loads <5000 copies/ml), in contrast to unselected HIV-infected HIV Vaccine trials Network (HVTN) participants. Viral inhibition of clade-matched HIV isolates was strongly correlated with the frequency of CD8+ T cells targeting vulnerable regions within Gag, Pol, Nef and Vif that had been identified in an independent study of nearly 1000 chronically infected individuals. These vulnerable and so-called “beneficial” regions were of low entropy overall, yet several were not predicted by stringent conservation algorithms. Consistent with this, stronger inhibition of clade-matched than mismatched viruses was observed in the majority of subjects, indicating better targeting of clade-specific than conserved epitopes. The magnitude of CD8+ T cell responses to beneficial regions, together with viral entropy and HLA class I genotype, explained up to 59% of the variation in viral inhibitory activity, with magnitude of the T cell response making the strongest unique contribution. However, beneficial regions were infrequently targeted by CD8+ T cells elicited by vaccines encoding full-length HIV proteins, when the latter were administered to healthy volunteers and HIV-positive ART-treated subjects, suggesting that immunodominance hierarchies undermine effective anti-HIV CD8+ T cell responses. Taken together, our data support HIV immunogen design that is based on systematic selection of empirically defined vulnerable regions within the viral proteome, with exclusion of immunodominant decoy epitopes that are irrelevant for HIV control.

Synthesis and antiviral activity of PB1 component of the influenza A RNA polymerase peptide fragments

This study is devoted to the antiviral activity of peptide fragments from the PB1 protein – a component of the influenza A RNA polymerase. The antiviral activity of the peptides synthesized was studied in MDCK cell cultures against the pandemic influenza strain A/California/07/2009 (H1N1) pdm09. We found that peptide fragments 6–13, 6–14, 26–30, 395–400, and 531–540 of the PB1 protein were capable of suppressing viral replication in cell culture. Terminal modifications i.e. N-acetylation and C-amidation increased the antiviral properties of the peptides significantly. Peptide PB1 (6–14) with both termini modified showed maximum antiviral activity, its inhibitory activity manifesting itself during the early stages of viral replication. It was also shown that the fluorescent-labeled analog of this peptide was able to penetrate into the cell. The broad range of virus-inhibiting activity of PB1 (6–14) peptide was confirmed using a panel of influenza A viruses of H1, H3 and H5 subtypes including those resistant to oseltamivir, the leading drug in anti-influenza therapy. Thus, short peptide fragments of the PB1 protein could serve as leads for future development of influenza prevention and/or treatment agents.

Anomeric selectivity and influenza A virus inhibition study on methoxylated analogues of Pentagalloylglucose

Anomeric selectivity in galloylation of d-glucose and d-mannose with carboxylic acid was explored under steglich conditions. Base catalyst 4-dimethylaminopyridine favored the formation of alpha-anomers, while adding an acid and carbodiimide favored the formation of beta-anomers. Steric hindrance between α,β-unsaturated acid and C-2 OH stereochemistry (adjacent carbon to anomeric) influenced anomeric selectivity for both d-glucose and d-mannose. The influenza A virus inhibition activities of the synthesized compounds were evaluated in Madin–Darby canine kidney cell line using the cytopathic effect inhibition assay. All the synthetic methoxylated analogues showed more considerable activity against influenza A virus than their corresponding acids, which indicated the sugar core as key functionality for anti-viral activity. The activities of trimethoxy-cinnamic acid Pentagalloylglucose analogues, 3α, 3β, 4α, and 4β (IC50, 109.1μM, 134.4μM, 119.5μM, 111.1μM, respectively) were better than those of trimethoxy-benzoic acid Pentagalloylglucose analogues, 1-αβ and 2α, 2β (IC50, 209.8μM, 132.9μM, 161.2μM, respectively), which suggested that the double bond in cinnamic acid Pentagalloylglucose analogues makes the major contribution for influenza A virus inhibitory activity. Notably, several anomeric mixtures showed better activities than pure alpha or beta anomer and were almost two times more effective than Ribavirin, a clinically used anti-viral drug.

Synthesis and evaluation of imidazole-4,5- and pyrazine-2,3-dicarboxamides targeting dengue and yellow fever virus

The results of a high-throughput screening assay using the dengue virus-2 replicon showed that the imidazole 4,5-dicarboxamide (I45DC) derivative (15a) has a high dengue virus inhibitory activity. Based on 15a as a lead compound, a novel class of both disubstituted I45DCs and the resembling pyrazine 2,3-dicarboxamides (P23DCs) were synthesized. Here, we report on their in vitro inhibitory activity against dengue virus (DENV) and yellow fever virus (YFV). Some of these first generation compounds have shown activity against both viruses in the micromolar range. Within this series, compound 15b was observed to display the highest antiviral potency against YFV with an EC50 = 1.85 μM. In addition, compounds 20a and 20b both potently inhibited replication of DENV (EC50 = 0.93 μM) in Vero cells.

A virus inhibitory protein isolated from Cyamopsis tetragonoloba (L.) Taub. upon induction of systemic antiviral resistance shares partial amino acid sequence homology with a lectin.

Two virus inhibitory proteins were purified from Cyamopsis tetragonoloba , induced to resist virus infections by CIP-29, a systemic resistance inducing protein from Clerodendrum inerme, and characterized. One of them shared homology with a lectin. CIP-29, a known 29 kDa systemic antiviral resistance inducing protein isolated from Clerodendrum inerme, has been used to induce systemic resistance in Cyamopsis tetragonoloba against Sunn-hemp rosette virus (SRV). Paper reports the detection of virus inhibitory activity in induced-resistant leaf sap of C. tetragonoloba, and the purification of two virus inhibitory agents (VIAs) thereof. VIA activity was recorded as a reduction in lesion number of SRV, Tobacco mosaic virus, and Papaya ringspot virus, when they were incubated separately with resistant sap and inoculated onto susceptible C. tetragonoloba, Nicotiana tabacum cv. Xanthi-nc, and Chenopodium quinoa, respectively. The two VIAs were isolated from resistant C. tetragonoloba plant leaves using combinations of column chromatography. Both were basic proteins, and since their M r was 32 and 62 kDa, these VIAs were called CT-VIA-32 and CT-VIA-62, respectively, on the basis of their molecular mass and the host. CT-VIA-62 displayed better activity, and was thus studied further. It tested positive for a glycoprotein, and was serologically detected only in leaf tissue post-induction. Tryptic peptides generated in-gel, post SDS-PAGE of CT-VIA-62, were sequenced through LC/MS/MS. All CT-VIA-62 peptides were found to share homologies with proteins from Medicago truncatula that possess a mannose-binding lectin domain.

Limited Impact of Passive Non-Neutralizing Antibody Immunization in Acute SIV Infection on Viremia Control in Rhesus Macaques

BackgroundAntiviral antibodies, especially those with neutralizing activity against the incoming strain, are potentially important immunological effectors to control human immunodeficiency virus (HIV) infection. While neutralizing activity appears to be central in sterile protection against HIV infection, the entity of inhibitory mechanisms via HIV and simian immunodeficiency virus (SIV)-specific antibodies remains elusive. The recent HIV vaccine trial RV144 and studies in nonhuman primate models have indicated controversial protective efficacy of HIV/SIV-specific non-neutralizing binding antibodies (non-NAbs). While reports on HIV-specific non-NAbs have demonstrated virus inhibitory activity in vitro, whether non-NAbs could also alter the pathogenic course of established SIV replication in vivo, likewise via neutralizing antibody (NAb) administration, has been unclear. Here, we performed post-infection passive immunization of SIV-infected rhesus macaques with polyclonal SIV-specific, antibody-dependent cell-mediated viral inhibition (ADCVI)-competent non-NAbs.Methods and FindingsTen lots of polyclonal immunoglobulin G (IgG) were prepared from plasma of ten chronically SIVmac239-infected, NAb-negative rhesus macaques, respectively. Their binding capacity to whole SIVmac239 virions showed a propensity similar to ADCVI activity. A cocktail of three non-NAb lots showing high virion-binding capacity and ADCVI activity was administered to rhesus macaques at day 7 post-SIVmac239 challenge. This resulted in an infection course comparable with control animals, with no significant difference in set point plasma viral loads or immune parameters.ConclusionsDespite virus-specific suppressive activity of the non-NAbs having been observed in vitro, their passive immunization post-infection did not result in SIV control in vivo. Virion binding and ADCVI activity with lack of virus neutralizing activity were indicated to be insufficient for antibody-triggered non-sterile SIV control. More diverse effector functions or sophisticated localization may be required for non-NAbs to impact HIV/SIV replication in vivo.

Characterization of Humoral and Cellular Immune Responses Elicited by a Recombinant Adenovirus Serotype 26 HIV-1 Env Vaccine in Healthy Adults (IPCAVD 001)

Adenovirus serotype 26 (Ad26) has been developed as a novel candidate vaccine vector for human immunodeficiency virus type 1 (HIV-1) and other pathogens. The primary safety and immunogenicity data from the Integrated Preclinical/Clinical AIDS Vaccine Development Program (IPCAVD) 001 trial, the first-in-human evaluation of a prototype Ad26 vector-based vaccine expressing clade A HIV-1 Env (Ad26.ENVA.01), are reported concurrently with this article. Here, we characterize in greater detail the humoral and cellular immune responses elicited by Ad26.ENVA.01 in humans. Samples from the IPCAVD 001 trial were used for humoral and cellular immunogenicity assays. We observed a dose-dependent expansion of the magnitude, breadth, and epitopic diversity of Env-specific binding antibody responses elicited by this vaccine. Antibody-dependent cell-mediated phagocytosis, virus inhibition, and degranulation functional activity were also observed. Env-specific cellular immune responses induced by the vaccine included multiple CD8(+) and CD4(+) T-lymphocyte memory subpopulations and cytokine secretion phenotypes, although cellular immune breadth was limited. Baseline vector-specific T-lymphocyte responses were common but did not impair Env-specific immune responses in this study. Ad26.ENVA.01 elicited a broad diversity of humoral and cellular immune responses in humans. These data support the further clinical development of Ad26 as a candidate vaccine vector. NCT00618605.

Synthesis and Biological Evaluation of Analogs of Methyl Ursolate 3-O-β-Chacotrioside as H5N1 Viral Entry Inhibitors

The earliest stage of influenza virus infection is the viral entry to the host cell. In our previous work, we discovered the first three small molecule H5N1 viral entry inhibitors 1–3. Here, based on saponin 3, methyl ursolate 3-O-β-chacotrioside, several analogs were synthesized and evaluated to understand the structure-activity relationships of this type of compound on the H5N1 viral entry inhibitory activity. The preliminary studies demonstrated that unlike saponins 1 and 2, it is possible to reduce the 3-O-chacotriosyl residue of compound 3 to a disaccharide without affecting the viral entry activities significantly. The results obtained will render new clues to the understanding of the antiviral profile for these types of compounds.

HSV IgG antibody inhibits virus detection in CSF

BackgroundBefore PCR testing of cerebrospinal fluid (CSF), laboratory diagnosis of herpes encephalitis (HSE) was based on virus isolation from brain biopsy. Viral isolation from CSF has limited clinical value due to low virus recovery; the cause for which has not been demonstrated. ObjectiveTo investigate the role of anti-HSV antibodies on recovery of HSV from CSF via cell culture. Study designHSV-positive CSF samples were evaluated for their ability to neutralize HSV in cell culture. The presence of HSV-specific IgG and IgM antibodies were analyzed using HSV-infected cells. To identify whether HSV-specific IgG is the cause of viral inhibition, IgG was removed using anti-human IgG magnetic beads. Viral inhibition from CSF originating from asymptomatic patients was examined as a comparison. ResultsCSF from 13 patients with acute HSV CNS disease was analyzed. All displayed high levels of viral neutralization to both HSV-1 and HSV-2 regardless of the infecting subtype. Interestingly, all the CSF samples stained strongly for anti-IgG antibody but none for anti-IgM antibody. Removal of IgG from CSF eliminated the viral inhibitory activity. Neutralizing IgG antibody was also found to be common in CSF of most patients, even in the absence of HSV disease. ConclusionsViral specific IgG is the major determinant of viral inhibition in CSF and prevents virus recovery in cell culture. In CSF from HSE un-infected patients, viral inhibitory IgG originates from circulating serum antibody and is commonly present in CSF. However, this inhibitory IgG is not protective for the development of HSV disease.