Efficacy and safety of Aviron Rapid® in 18-60-year-old patients with clinical diagnosis of acute respiratory viral infection: a multicenter, randomized, double-blind, placebo-controlled clinical trial.

AIM: Prevention and treatment of upper respiratory tract infections are given the highest priority because of the tremendous health and economic impact of these diseases. Development of novel effective and safe options for treatment can contribute considerably to decrease the burden of disease. MATERIALS AND METHODS: We designed a multicenter, randomized, double-blind, placebo-controlled study in ambulatory-treated adult patients with a clinical diagnosis of acute upper respiratory tract viral infection. The patients (18-60 years old) were randomized into two groups and followed-up for 5 days. Group 1 received the standard symptomatic therapy + Aviron Rapid®, and Group 2 received the standard symptomatic therapy + placebo. The primary endpoint of the study was defined as the duration of disease measured by the percentages of disease-free patients for every 12-hour period of the study. RESULTS: Treating clinically relevant patients with the natural product Aviron Rapid® for 5 days decreases the duration of disease, the intake of antipyretics and the severity of symptoms. Significant difference between the tested groups for most of studied parameters was found as soon as 12 or 24 hours after initiation of administration in favour of active arm and was the most prominent on days 3 and 4. Significant decrease in the total score of symptoms severity was achieved on day 4 and extended to the end of study. There were no dif-ferences in the adverse events between the groups and the tested product demonstrated excellent safety profile. CONCLUSIONS: This study is a clinical confirmation of well documented antiviral activity of the product targeting multiple points in viral replication and covering broad spectrum viral pathogens.

JC polyomavirus in the aetiology and pathophysiology of glial tumours.

Glial brain tumours with their poor prognosis, limited treatment modalities and unclear detailed pathophysiology represent a significant health concern. The purpose of the current study was to investigate and describe the possible role of the human polyomavirus JC as an underlying cancerogenic or co-cancerogenic factor in the complex processes of glial tumour induction and development. Samples from 101 patients with glial tumours were obtained during neurosurgical tumour resection. Small tissue pieces were taken from several areas of the histologically verified solid tumour core. Biopsies were used for DNA extraction and subsequent amplification reactions of sequences from the JC viral genome. Real-time polymerase chain reaction was used for detection and quantification of its non-coding control region (NCCR) and gene encoding the regulatory protein Large T antigen (LT). An average of 37.6% of all patients was found to be LT positive, whereas only 6.9% tested positive for NCCR. The analysis of the results demonstrated significant variance between the determined LT prevalence and the rate for NCCR, with a low starting copy number in all positive samples and threshold cycles in the range of 36 to 42 representing viral load in the range from 10 to 1000 copies/µl. The results most probably indicate incomplete JC viral replication. Under such conditions, mutations in the host cell genome may be accumulated due to interference of the virus with the host cell machinery, and eventually malignant transformation may occur.

Prevalence of JC polyomavirus genomic sequences from the large T-antigen and non-coding control regions among Bulgarian patients with primary brain tumors.

A total of 111 fresh brain biopsies from patients with primary brain tumors were examined for JC polyomavirus sequences from the Large T antigen encoding region (LT) and the viral non-coding control region (NCCR). SYBR Green and TaqMan real-time polymerase chain reaction assays were used. In the glioblastoma group of 39 patients 48.7% were positive for LT sequences. Among the astrocytoma group (19 patients) and the oligodendroglioma group (12 patients) 31.6% and 33.3% were also positive. The prevalence of LT genomic sequences among the other groups was as follows: in 2 out of 3 oligoastrocytomas; in 3 out 5 gangliogliomas; in 2 out of 5 meduloblastomas; in 1 out 3 pineocytomas; and in none of the tested 5 ependimomas. All positive samples had a late threshold cycle that varied from 36 to 49, indicative of very low starting viral number. Only 21 of all the 111 samples were positive for NCCR. Low copy number in range of 10-1,000 was present. Notably, only 8 of all NCCR positive specimens were also LT positive. It might be suggested that the disproportion between the results for LT and NCCR is either due to clonally integrated LT fragments, with loss of genetic material, or changes in the NCCR. The latter would alter the productive course of the infection and may establish a premise for continuous interaction of viral regulatory proteins with cell molecules that are responsible for the control of the cell cycle. This may lead subsequently to malignant transformation.

Do human polyoma viruses and human immunodeficiency virus share common co-receptors?

Host and/or viral factors involved in human polyomavirus (HPoV) infection in persons living with HIV remain unknown. A hypothesis is outlined suggesting the importance of the co-receptors CCR5, CCR2, and CXCR4 not only for HIV, but also for HPoV. Functionally capable receptors coded by wild-type (wt) genotypes could facilitate internalization of HPoV in the cell resulting in brain and/or kidney infection/s in HIV infected individuals. Forty-nine Bulgarians with HIV, all treated by HAART, without neurological and/or kidney disorders, were tested for JCV and BKV and genotyped for CCR5 (CCR5del32), CCR2 (CCR2-64I), and CXCR4 (SDF1-3'A). In 27/49 (55.1%) individuals a co-infection with HPoV was identified-BKV in 12/49 (24.5%), JCV-in another 12/49 (24.5%), and both viruses-in 3/49 (6.1%). A high frequency of wt CCR5 was found in patients with HPoV (91.7% for BKV and JCV and in 100% with both viruses). V/V of CCR2 was presented in 75% for BKV and JCV and in 66.7% for BKV plus JCV. SDF1-3'G/G predominated in JCV infected patients (75%), while G/A and A/A genotypes were more frequent in patients with BKV (41.7%). Also, 21/22 (95.4%) persons without HPoV infection were heterozygous for SDF1 and CCR2. The number of individuals bearing wt of all co-receptors in the group of persons not infected with HPoV was lower (P = 0.03) than that with polymorphism/s in one or two genes (SDF1 and CCR2) in the same group. The results suggest a probable role of co-receptors used by HIV to facilitate infection with HPoV.

Sequence variations of the VP1 gene of Polyomavirus hominis 1 among Bulgarians.

Polyomavirus hominis 1 (BK virus, BKV) is an important pathogen in the field of transplantation medicine. BKV reactivation among renal-transplant recipients could cause BK associated nephropathy, which has unfavorable prognosis and is a cause for graft rejection. It is not clear why only few transplanted patients develop BK associated nephropathy while most exhibit asymptomatic viruria. One of the possible reasons lies in the mutations of the VP1 gene, encoding the main structural protein, bearing important determinants for the recognition of specific cellular receptors. The change of amino acid sequence could result in altered pathogenicity of BKV. The amplified sequences of BK in this research were from urines of patients with various clinical conditions along with healthy individuals. Nevertheless the sequence analysis which was undertaken did not show correlation between the viral genotype and the clinical condition. It was demonstrated that the most common BKV genotype in Bulgaria is genotype I and that the strains common in Bulgaria (genotypes I and IV) have typical European origin. Most of the sequenced BKV DNA samples (8/10) were correlated with the highest degree of similarity (81%) to the subcluster Ib. A specific place among the samples is taken by Pr-9, amplified from the urine of a pregnant woman that has a different evolutionary origins and might establish the beginning of a new distinct BKV strain.

Reactivation of Polyomavirus hominis 1 (BKV) during pregnancy and the risk of mother-to-child transmission.

BACKGROUND: Pregnancy is associated with down-regulation of immune responses of the mother. This might lead to reactivation and vertical transmission of latent viral infections such as BK virus (BKV). OBJECTIVES: To determine the presence of BKV in the urine of pregnant women and in cord blood at delivery. STUDY DESIGN: We examined urines from 52 pregnant women and 51 cord blood samples for BKV by real-time SYBR green PCR. RESULTS: BKV DNA was found in the urine of 18 (34.6%) pregnant women. No BKV DNA was detected by SYBR green PCR in the cord blood specimens. CONCLUSIONS: BKV reactivation is common during pregnancy but this is not associated with BKV in cord blood.

Identification of HPV DNA in patients with juvenile-onset recurrent respiratory papillomatosis using SYBR Green real-time PCR.

OBJECTIVE: Recurrent respiratory papillomatosis (RRP) is the most common benign neoplasm affecting the larynx and upper respiratory tract in children. Human papillomavirus (HPV) has been implicated as the cause of RRP, most commonly types 6 and 11. The present study was undertaken to evaluate the occurrence of HPV types in a group of patients with juvenile-onset RRP (JORRP). METHODS: The study group consists of 23 patients with JORRP. The clinical records of the patients were reviewed, and JORRP was classified as non-aggressive or aggressive. The laryngeal biopsies were taken and investigated for HPV DNA presence using real-time polymerase chain reaction (PCR) with a set of consensus primers (MY09/11). Viral typing was subsequently performed by real-time PCR with type-specific primers for HPV types 6, 11, 16, 18, 31, and 33. RESULTS: HPV presence was detected in all samples with amplifiable DNA. HPV-11 was revealed in 61.9% of the patients and HPV-6 in 23.8%. Double positivity for HPV types 6 and 11 was identified in 14.3%. Our findings suggest that RRP runs a more aggressive clinical course when HPV-11 infection is present (p=0.0265). CONCLUSIONS: Our results suggest a high frequency of HPV infection in the upper respiratory tract of the studied patients. We believe that the routine application of molecular techniques such as PCR for detection and analysis of HPVs in patients with RRP has diagnostic and prognostic significance.

Productos naturales del bosque humedo tropical de Venezuela, inhibidores de la replicacion de VIH-1 / Natural products from the amazonian rainforest of Venezuela as inhibitors of HIV-1 growth

More than 100 plant extracts from the Amazonian rain forest of Venezuela were evaluated for their cytotoxicity and inhibitory activity against the human immunodeficiency virus type-1 (HIV-1). Aqueous extracts from Fomitella supina (S # 0389-4), Phellinus rhabarbarinus (S # 0389-7), Trichaptum perrottetti (S # 0389-8) and Trametes cubensis (S # 0389-13), Polyporaceae exhibited strong anti-HIV-1 activity, without toxicity for Molt-4 lymphocytic cells. Our results demonstrated, that the compound(s) acted by mechanism of direct virion inactivation and by inhibition of syncytium formation in an in vitro culture system. These results support the suggestion that the test extracts specifically act at the level of CD4-gp120 binding. The active components of these extracts is at present unknown, but anti-AIDS agents, such as those found in this study, individually or in combination, may be of therapeutic relevance