Intervirology (Intervirology )

Publisher: S. Karger (Firm), Karger


As its title suggests, ëIntervirologyí covers progress in both basic and clinical virus research, and aims to provide a forum of exchange among the various disciplines within virology. Issues publishing original papers alternate with thematic issues, focusing on one clearly defined topic of basic or medical virology. This thematic concentration serves to make timely reviews, research reports and controversy easily accessible to both specialists in the field and those who want to keep track of the latest developments outside their own area of interest. The scope encompasses work on the molecular biology of animal viruses, including genome organization and regulation, and the structure and function of viral proteins. The pathogenesis, immunology, diagnosis and prophylaxis of viral diseases are discussed, with attention also given to virus-like agents such as prions and viroids.

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    Intervirology (Online)
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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The long-term administration of a nucleos(t)ide analogue (NA) for the treatment of chronic hepatitis B may encourage the emergence of viral mutations associated with drug resistance. Minor populations of viruses may exist before treatment, but are difficult to detect because of technological limitations. Identifying minor viral quasispecies should be useful in the clinical management of hepatitis B virus (HBV) infection. Methods: Six treatment-naïve Indonesian patients with chronic HBV infection participated in this study. The polymerase region of the HBV genome, including regions with known drug-resistant mutations, was subjected to capillary sequencing and MiSeq sequencing (Illumina). Mutations were analyzed with Genomics Workbench software version 6.0.1 (CLC bio). Results: The mean mapping reads for the six samples was 745,654, and the mean number of amplified fragments ranged from 17,926 to 25,336 DNA reads. Several known drug-resistant mutations in the reverse transcriptase region were identified in all patients, although the frequencies were low (0.12-1.06%). The proportions of the total number of reads containing mutations I169L/M, S202R, M204I/L or N236S were >1.0%. Conclusion: Several known NA-resistant mutations were detected in treatment-naïve patients in Indonesia using deep sequencing. Careful management of such patients is essential to prevent drug-resistant mutations from spreading to other patients. © 2014 S. Karger AG, Basel.
    Intervirology 10/2014; 57(6):384-392.
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    ABSTRACT: Objective: Sandfly fever phleboviruses are endemic in Mediterranean countries. We report a febrile phlebovirus case in a Greek patient who presented signs of neuroinvasive infection. Methods: In summer 2010, a 20-year-old male was admitted to hospital with fever and lethargy; he was a resident of central Macedonia, northern Greece, where a large outbreak of West Nile virus (WNV) infections occurred at that time. Since there was no laboratory evidence of WNV infection, the patient's serum and cerebrospinal fluid were tested for a probable phlebovirus infection. Results: High titers of IgM and IgG antibodies against Toscana virus were detected in serum and cerebrospinal fluid, while the titers against sandfly fever Naples virus were lower; no reactivity was detected against sandfly Sicilian and Cyprus viruses. Since neutralization assays were not performed and PCR resulted in being negative, it was concluded that the causative agent was a phlebovirus of the sandfly fever Naples serocomplex. Conclusion: The present case confirms results from previous seroprevalence studies showing that phleboviruses of the sandfly fever Naples serocomplex are present in Greece and provides evidence that they cause febrile neuroinvasive disease in humans, prompting for inclusion of phleboviral infections in the differential diagnosis of acute febrile cases during the time when sandflies are active. © 2014 S. Karger AG, Basel.
    Intervirology 10/2014; 57(6):393-395.
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    ABSTRACT: Background: Low pathogenic H9N2 avian influenza virus (AIV) has been spreading worldwide, leading to huge economic losses to poultry husbandry, but few studies were concerned about its aerosol infection. Methods: This study compared the infective doses of H9N2 AIV to chickens by three different routes, aerosol infection, intranasal and gastrointestinal infection, and determination of the results was conducted by detecting virus shedding and seroconversion of chickens. Results: The results indicated that chickens were susceptible to H9N2 AIV with a different infection rate which depended on the route of inoculation. H9N2 AIV media aerosol-infective dose (aID50) to chickens was about 491 TCID50, intranasal infection was 398 TCID50, and gastrointestinal infection was 19,952 TCID50. Conclusion: The infection ability of H9N2 AIV to chickens was related to its way of invading. The respiratory infection ability was about 40 times more effective than gastrointestinal infection, which suggested that urgent attention should be paid to environmental disinfection to block airborne transmission of influenza virus. © 2014 S. Karger AG, Basel.
    Intervirology 10/2014; 57(6):369-374.
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    ABSTRACT: The aim of this study was to explore the prevalence of basal core promoter (BCP) and precore gene (PC) mutations in hepatitis B virus (HBV) isolates among the Nicobarese tribe and their relationship with genotypes and HBeAg status. A total of 726 blood samples were collected from two villages of the Car Nicobar Island where mass vaccination was performed in the year 2000. HBV DNA was isolated and the BCP and PC regions were amplified and sequenced directly. The samples positive for HBV DNA were tested for HBsAg, HBeAg and anti-HBe. Among the 211 and 515 samples collected from vaccinated and nonvaccinated persons, 16 and 82 were positive for HBV DNA, respectively. Among the vaccinated individuals, only 1 had a mutation in both the BCP and PC gene. Among the nonvaccinated subjects, 3 (4.5%) had an A1762T mutation, 8 (12.1%) had a G1764A mutation, 11 (16.7%) had a G1896A mutation and 4 (6.1%) had a G1899A mutation. The HBeAg-negative subjects had a significantly higher frequency of BCP and PC mutations than the HBeAg-positive subjects. The prevalence of a PC mutation was higher than that of a BCP mutation. The present study stresses the need for the continuous surveillance of subjects with BCP and PC mutations, as the mutations may contribute to the progression of liver disease. © 2014 S. Karger AG, Basel.
    Intervirology 10/2014; 57(6):357-364.
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    ABSTRACT: Introduction: Chronic inflammations including infectious disorders such as HIV infection are now considered as risk factors for atherosclerosis. In this study, conducted for the first time on human subjects, human T-lymphotropic virus type 1 (HTLV-1) infection was examined as a potential risk factor for atherosclerosis. Materials and Methods: This is a matched-pair cross-sectional study on 58 HTLV-1-infected cases and 55 healthy control subjects. The subjects did not have any major cerebrovascular risk factors. Carotid intima-media thickness (IMT) was measured for each patient using the standard protocol of the Atherosclerosis Risk in Communities (ARIC) Study. Results: The mean age of the subjects was 42.9 ± 10.52 years, and males made up 33% of the population. The difference between the mean IMT of the infected case group and that of the healthy control group was significant (p < 0.05). Discussion: This study indicated that the HTLV-infected individuals showed a greater carotid IMT than the age- and sex-matched control subjects. Observing no other known risk factor for atherosclerosis, we concluded that this significant difference in IMT might support the hypothesis that HTLV-1 infection is an independent risk factor for atherogenesis. © 2014 S. Karger AG, Basel.
    Intervirology 10/2014; 57(6):365-368.
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    ABSTRACT: Objective: The mouse mammary tumor virus (MMTV) is the well-established etiological agent of mammary tumors in mice. A series of studies have implicated that a human murine mammary tumor virus-like virus occurs in human breast cancer, but it is unclear whether it has any causal role. Methods: The aim of the present study was to investigate the presence of MMTV env gene-like sequences in a group of Iranian women with or without breast cancer. A total of 65 breast cancer and 65 noncancerous breast specimens from the Department of Pathology of Tabriz University in East Azerbaijan, Iran, were analyzed by nested PCR. Results: All breast cancer and benign breast samples were negative for MMTV env gene-like DNA. Conclusion: These results indicate that the MMTV env gene-like virus may not play a significant role in the etiology of breast cancer among Iranian women. © 2014 S. Karger AG, Basel.
    Intervirology 10/2014; 57(6):353-356.
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    ABSTRACT: Objective: To genetically characterize human influenza viruses and their susceptibilities to antivirals during two post-pandemic seasons in Lebanon. Methods: Influenza virus was isolated from nasopharyngeal swabs that were obtained from patients with influenza-like illness during 2010-2012 and further analyzed both phenotypically and genotypically. Results: During the 2010-2011 season, both 2009 pandemic H1N1 (H1N1p) and B viruses co-circulated with equal prevalence, while the H3N2 virus predominated during the 2011-2012 season. All H3N2 and H1N1 viruses were resistant to amantadine. Importantly, all viruses of the influenza A and B types were susceptible to the neuraminidase (NA) inhibitors oseltamivir, zanamivir, peramivir, and laninamivir. Nonetheless, all 2011-2012 H1N1p isolates had three mutations (V241I, N369K, and N386S) in the NA gene that were suggested to be permissive of the H275Y mutation, which confers resistance to oseltamivir. We also detected one H1N1p virus during the 2010-2011 season with a 4-fold decrease in susceptibility to oseltamivir due to an NA-S247N mutation. This isolate was phylogenetically distinct from other H1N1p viruses that were isolated in other regions. Conclusions: Influenza A viruses with reduced susceptibility to oseltamivir and mutations permissive for acquiring NA resistance-conferring mutation with minimal burden on their fitness were isolated in Lebanon. © 2014 S. Karger AG, Basel.
    Intervirology 10/2014; 57(6):344-352.
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    ABSTRACT: Objectives: This study investigated the antiviral efficacy of adefovir (ADV) rescue therapy and the feasibility of lamivudine (LAM) discontinuation in LAM-resistant chronic hepatitis B (CH-B) patients who had attained a virological response (VR) with LAM + ADV combination therapy. Methods: The VR and virological breakthrough (VBT) were analyzed in 106 consecutively enrolled LAM-resistant CH-B patients who received ADV rescue therapy during a mean follow-up period of 55.2 months. Seventy-four patients achieved VR, and were divided into the LAM-discontinuation group (n = 39) and the LAM-continuation group (n = 35). The VR and VBT between the 2 groups were compared. Results: For all 106 LAM-resistant CH-B patients, the overall cumulative probabilities of VR at 1, 2, 3 and 5 years of ADV rescue therapy were 40.6, 55.7, 64.6 and 81.3%, respectively. The cumulative probabilities of VBT at 1, 2, 3 and 5 years were 0, 2.9, 8.8 and 13.9%, respectively. Whether they discontinued or continued LAM after achieving VR on LAM + ADV therapy, VR and VBT were not significantly different during a mean follow-up period of 40.4 months. Conclusions: There was a good long-term VR with ADV rescue therapy for LAM-resistant CH-B patients. Moreover, discontinuing LAM was found to be feasible for patients who attained VR during ADV + LAM therapy. © 2014 S. Karger AG, Basel.
    Intervirology 09/2014; 57(6):337-343.
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    ABSTRACT: Merkel cell polyomavirus (MCPyV) large T antigen (LT-ag) is frequently found truncated in Merkel cell carcinomas (MCC) and it is considered a major tumor-specific signature. Nonetheless, the biological role of LT-ag nontruncated mutations is largely unknown. In this study, MCPyV LT-ag second exon from 11 non-MCC oral samples and NCBI sequences derived from different anatomical sites were studied from the genetic and structural standpoint. As expected, the LT-ag mutation profile was influenced by the geographical origin of the sample, although nonsynonymous mutations were more frequent in lesional tissues. Our in silico study suggests that the mutations found would not significantly affect protein functions, regardless of sample category. This work presents a thorough investigation of the structural and functional properties of LT-ag nontruncated mutations in MCPyV. Our results sustain the geographical influence of the MCPyV genetic profile, but do not discard genetic tissue specificities. Further investigation involving other genetic segments in healthy and lesional tissues are necessary to improve our knowledge on MCPyV pathogenesis. © 2014 S. Karger AG, Basel.
    Intervirology 09/2014; 57(6):331-336.
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    ABSTRACT: Background: We previously attenuated the infectious bronchitis virus (IBV) strain CK/CH/LDL/97I and found that it can convey protection against the homologous pathogenic virus. Objective: To compare the full-length genome sequences of the Chinese IBV strain CK/CH/LDL/97I and its embryo-passaged, attenuated level to identify sequence substitutions responsible for the attenuation and define markers of attenuation. Methods: The full-length genomes of CK/CH/LDL/97I P5 and P115 were amplified and sequenced. The sequences were assembled and compared using the MEGALIGN program (DNAStar) and a phylogenetic tree was constructed using MEGA4 software. Results: The CK/CH/LDL/97I virus population contained subpopulations with a mixture of genetic mutants. Changes were observed in nsp4, nsp9, nsp11/12, nsp14, nsp15, nsp16, and ORF3a, but these did not result in amino acid substitutions or did not show functional variations. Amino acid substitutions occurred in the remaining genes between P5 and P115; most were found in the S region, and some of the nucleotide mutations resulted in amino acid substitutions. Among the 9 nsps in the ORF1 region, nsp3 contained the most nucleotide substitutions. Conclusions: Sequence variations in different genes, especially the S gene and nsp3, in the genomes of CK/CH/LDL/97I viruses might contribute to differences in viral replication, pathogenicity, antigenicity, immunogenicity, and tissue tropism. © 2014 S. Karger AG, Basel.
    Intervirology 08/2014; 57(6):319-330.
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    ABSTRACT: Human immunodeficiency virus type 1 (HIV-1) genetic diversity is one of the most important features of HIV-1 infections and the result of error accumulation during reverse transcription and of high viral turnover. HIV-1 reverse transcription is influenced by factors such as the level of nucleotides and/or the cellular activation state. HIV-1 diversity was investigated after 48 h of viral propagation in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors in three different cell culture conditions: (1) resting PBMCs, (2) simultaneous infection and PBMC activation, and (3) PBMC activation 72 h before infection. Cellular DNA was extracted and proviruses of each culture condition were amplified. Single-genome PCR clones were obtained and the protease and reverse transcriptase of the pol gene were sequenced. An elevated number of nucleotide substitutions in all three culture conditions were observed. In condition 1, the mutational rate observed ranged from 1.0 × 10(-3) to 2.1 × 10(-2), the genetic diversity was 0.6%, and hypermutation was observed in 7.1% of sequenced clones. In condition 2, the mutational rate ranged from 1.0 × 10(-3) to 1.0 × 10(-2), the genetic diversity was 0.8%, and hypermutation affected 6.7% of clones. In condition 3, the mutational rate ranged from 2.8 × 10(-3) to 1.1 × 10(-2), the genetic diversity was 1%, and 5.9% of clones were hypermutated. Substitutions occurred more frequently in some specific nucleotide stretches, and a common pattern for substitutions in all the different conditions was identified. There was a significant accumulation of mutations during the initial periods of in vitro HIV-1 propagation irrespective of culture conditions. The rapid accumulation of virus diversity might represent a viral strategy when colonizing new hosts. Complementary studies are necessary to allow for a better understanding of the initial periods of infection, which represent a crucial event related to disease progression. © 2014 S. Karger AG, Basel.
    Intervirology 06/2014; 57(5):277-288.
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    ABSTRACT: Objectives: Patients with chronic hepatitis B virus (HBV) may exhibit significant liver pathology despite alanine aminotransferase (ALT) and HBV DNA levels below the cutoff values advised by treatment guidelines. We evaluated candidacy for HBV therapy when baseline histopathological changes are taken into consideration. Methods: Clinical, biochemical, serological, virological, and histopathological (METAVIR score) data of 117 patients with HBeAg-negative chronic HBV genotype D were collected and analyzed. Results: Significant pathology (≥F2 and/or ≥A2) and fibrosis (≥F2 ± ≥A2) were found in 73 (62.4%) and 59 (50.4%) patients, respectively. Based on HBV DNA (>2,000 IU/ml) and ALT levels >2 × 40 U/l (the standard cutoff value), only 31 (26.5%) patients were candidates for therapy. This increased to 58 (49.6%) patients when the new ALT cutoff values (30 U/l for males, and 19 U/l for females) were applied. Relying on either ≥F2 and/or A ≥2 or ≥F2 ± ≥A2 increases the treatment candidacy to 73 (62.4%) and 59 (50.4%) patients, respectively. Also, when compared with standard ALT cutoff values, applying both new ALT cutoff values with either significant pathology or fibrosis increases treatment candidacy to 28 (23.9%) and 42 (35.9%) patients, respectively. Conclusion: Liver pathology is more reliable than ALT and HBV DNA in the decision to treat patients with HBeAg-negative chronic HBV genotype D. © 2014 S. Karger AG, Basel.
    Intervirology 06/2014; 57(5):248-253.
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    ABSTRACT: Objectives: Highly-active antiretroviral therapy (HAART) was scaled up in Guangxi, China in 2005. The number of individuals receiving free HAART increased dramatically from June 2010 under the Guangxi Government's anti-HIV programme. We aimed to determine the prevalence of HIV-transmitted drug resistance (TDR) of Guangxi. Methods: HIV-positive, antiretroviral-naive individuals were recruited from the east (Hezhou), south (Qinzhou), west (Baise), north (Guilin) and centre (Laibin) of Guangxi. The pol gene of the virus from the individuals was analysed. Results: The overall prevalence of HIV TDR was 3.2% (7/216, 95% CI 0.9-5.5). The prevalence rates in Baise, Guilin, Hezhou, Qinzhou and Laibin are 4.9% (2/41, 95% CI -1.7 to 11.5), 2.3% (1/44, 95% CI -2.1 to 5.7), 4.7% (2/43, 95% CI -1.6 to 11.0), 2.6% (1/38, 95% CI -2.5 to 7.7) and 2.0% (1/50, 95% CI -1.9 to 5.9), respectively. No significant difference in the prevalence was found among them. No factors were found to be associated with TDR, including CD4 cell counts, viral loads and genotypes. The subtypes CRF01_AE, CRF07_BC, CRF08_BC and B were found. Subtype CRF08_BC is the predominant subtype in Baise while CRF01_AE is the predominant subtype elsewhere in Guangxi. Conclusions: The prevalence of TDR in antiretroviral-naive patients in Guangxi remains low 8 years after scale-up of HAART. © 2014 S. Karger AG, Basel.
    Intervirology 06/2014; 57(5):270-276.
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    ABSTRACT: Objective: This study was designed to prospectively evaluate the antiviral responses and evolution of resistance mutations during adefovir (ADV) plus lamivudine (LMV) therapy in patients with entecavir (ETV)-resistant hepatitis B virus (HBV) infection. Methods: Twenty chronic hepatitis B (CHB) patients who had been receiving ETV for more than 6 months and developed virologic breakthrough due to ETV resistance were consecutively enrolled. Results: Patients received ADV plus LMV therapy for 12 months. The baseline mean serum HBV DNA level was 5.59 ± 1.28 log10 IU/ml. The rtT184L/I/A/F (50%), rtS202G (25%) and mixed ETV-resistant mutations (25%) were detected at enrollment. The mean reduction in serum HBV DNA levels from baseline to 12 months was -2.3 ± 1.06 log10 IU/ml (p < 0.001). Seventeen patients were followed up for the full 12 months, and complete virologic response (HBV DNA <20 IU/ml) was observed in 4 patients (23.5%). Among the remaining 13 patients who still had detectable HBV DNA, 7 patients showed disappearance of ETV-resistant mutations or reduction of the proportion of ETV-resistant mutants. An ADV- and LMV-resistant mutant (rtA181T) emerged in 2 patients (11.7%). Conclusions: ADV plus LMV combination therapy suppresses ETV-resistant mutants in the viral population and significantly reduces serum HBV DNA levels in ETV-resistant CHB patients. © 2014 S. Karger AG, Basel.
    Intervirology 06/2014; 57(5):239-247.
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    ABSTRACT: Objective: We report the infection of New Zealand white rabbits with Epstein-Barr virus (EBV). Methods: EBV prepared in B95-8 (producer) cells was inoculated to rabbits by combined intranasal and oral routes. Blood and white blood cell (WBC) samples were taken before infection, then on days 8, 28 and 98 post-infection (p.i.). Results: Administration of either 3 × 10(8) (group A, 11 rabbits) or 1 × 10(9) (group B, 10 rabbits) EBV DNA copies per animal induced subacute and/or persistent infection. The IgG antibodies in plasma were detected by ELISA as well as by immunoblot (IB). The IB bands showed mainly antibodies to the BZRF1/Zta transactivation polypeptide (69.2%), the p54 early protein (53.4%) and to the p23 capsid protein (35.8%). No anti-EBNA1 antibody was detected throughout. Viral DNA could be detected by PCR in WBCs and/or spleen of 7 out of 21 infected rabbits (30%), while 60-80% of them showed serologic response. The transiently present EBV DNA was accompanied by LMP1 antigen. Conclusions: Rabbits developed persistent EBV infection in the absence of EBNA1 antibodies and by the lack of typical infectious mononucleosis-like syndrome. The absence of EBNA1 antibody may reflect the lack of EBNA1 in B cells of EBV-inoculated rabbits. © 2014 S. Karger AG, Basel.
    Intervirology 06/2014; 57(5):254-269.
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    ABSTRACT: Objective: Some patients with chronic hepatitis C virus (HCV) infection fail to achieve complete early virologic response (EVR) despite a marked decrease in HCV RNA at 4 weeks. We investigated the characteristics and final treatment outcomes of this patient subpopulation. Methods: A total of 516 patients with HCV genotype 1 were enrolled. Background characteristics and final outcomes were compared between patients who achieved complete EVR and those who did not among patients whose HCV RNA levels decreased 3.0 log10 or more at 4 weeks. Results: 78 of 334 patients (23.4%) with a ≥3.0 log10 reduction in HCV RNA levels at 4 weeks failed to achieve complete EVR. Female sex, higher pretreatment HCV RNA levels and lower baseline alanine aminotransferase (ALT) activity were independently associated with failure of complete EVR. The rate of sustained virologic response (SVR) in patients without complete EVR was 47.4%, significantly lower than that in patients with complete EVR (89.7%, p < 0.0001). Conclusions: Female patients, patients with higher pretreatment HCV RNA levels and patients with lower baseline ALT have a high likelihood of failure of complete EVR even when they had a ≥3 log10 reduction of HCV RNA at 4 weeks, resulting in a significantly lower SVR rate. © 2014 S. Karger AG, Basel.
    Intervirology 06/2014; 57(5):289-296.
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    ABSTRACT: Background: Herpesviridae encode a family of protein homologues that function as the 'port of entry' for insertion of the viral DNA into preformed capsids during encapsidation. Methods: Transmission electron microscopy (TEM) of recombinant varicella-zoster virus pORF54 was performed. Results: Results suggest that pORF54 forms higher-order structures with itself. Enriched fractions analyzed by TEM revealed non-axial oriented portals with defined central channels and distinguishable crown, wing and clip regions. Conclusion: These morphological features are consistent with those previously reported for other herpesvirus and bacteriophage portal proteins. © 2014 S. Karger AG, Basel.
    Intervirology 03/2014; 57(2):121-125.