Characterization of the anti‐HBV activity of HLP1–23, a human lactoferrin‐derived peptide

Lactoferrin (Lf) was shown to exhibit its antiviral activity at an early phase of viral infection and a mechanism whereby the protein interacts with host cell surface molecules has been suggested. In this study, human Lf (HLf) and seven HLf‐derived synthetic peptides (HLP) corresponding to the N‐terminal domain of the native protein (1–47 amino acids sequence) were assayed for their capacity to prevent hepatitis B virus (HBV) infection and replication using the HepaRG and HepG2.2.2.15 cell lines. Of the series tested, four peptides showed 40–75% inhibition of HBV infection in HepaRG cells, HLP_1–23, containing the GRRRR cationic cluster, being the most potent. Interestingly, this cluster is one of the two glycosaminoglycan binding sites of the native HLf involved in its antiviral activity; however, the mechanism of the HLP_1–23 action was different from that of the full‐length protein, the peptide inhibiting HBV infection when pre‐incubated with the virus, while no effect was observed on the target cells. It is suggested that the cationic cluster is sufficient for the peptide to interact stably with negatively charged residues on the virion envelope, while the absence of the second glycosaminoglycan binding site prevents its efficient attachment to the cells. In conclusion, this peptide may constitute a non‐toxic approach for potential clinical applications in inhibiting HBV entry by neutralizing the viral particles. J. Med. Virol. 85:780–788, 2013. © 2013 Wiley Periodicals, Inc.     

Switching to darunavir/ritonavir 800/100 mg once‐daily containing regimen maintains virological control in fully suppressed pre‐treated patients infected with HIV‐1

The objective of this study was to evaluate the switch to once‐daily darunavir/ritonavir 800/100 mg in treatment‐experienced patients with suppressed HIV‐1 replication on a twice‐daily ritonavir‐boosted protease‐inhibitor (bid PI/r) containing regimen, that is in a setting where genotypic resistance test cannot be performed. In this open label, non‐comparative, multicenter study, patients on a bid PI/r‐containing triple combination, with suppressed viral replication, were switched to once‐daily darunavir/r 800/100 mg containing triple combination. The primary endpoint was the proportion of patients with plasma HIV‐RNA < 50 copies/ml 24 weeks after the switch. Intensive darunavir pharmacokinetic evaluation was performed at Week 4 (W4) in 11 patients. Eighty‐five patients were enrolled. All had HIV‐RNA < 50 copies/ml at screening with a pre‐exposure to a median of 2 PI/r (1–5). By intent‐to‐treat analysis (missing = failure), 78/85 patients (92%, 95% CI [83;96]) maintained an HIV‐RNA < 50 copies/ml at W24. Seven patients experienced protocol‐defined treatment failure between baseline and W24: Two had confirmed low‐level viral rebound, one discontinued study treatment for adverse event, three withdrew their consent, and one was lost to follow‐up. By on‐treatment analysis, 78/80 patients (97%, 95% CI [91;99]) maintained an HIV‐RNA < 50 copies/ml at W24. Results were similar at Week 48. The median area under the darunavir plasma concentration–time curve measured in 11 patients was 61,380 ng hr/ml; darunavir median trough concentration 1,340 ng/ml and darunavir half‐life was 12.2 hr. Tolerability of once‐daily darunavir/r 800/100 mg was excellent. Optimally suppressed, treatment‐experienced patients can switch safely from a twice‐daily PI/r regimen to a once‐daily darunavir/r 800/100 mg containing regimen. J. Med. Virol. 85:8–15, 2012. © 2012 Wiley Periodicals, Inc.     

Monitoring of KI and WU polyomaviruses in hematopoietic stem cell transplant patients

Primary infection with KIPyV and WUPyV polyomaviruses occurs early in childhood followed by lifelong persistence in the body. Polyomavirus reactivation can occur in the presence of impaired immunity as in hematological malignancies or during immunosuppresssion induced by medications. In this study, reactivation of KIPyV and WUPyV was monitored by conventional PCR in plasma samples of 26 stem cell transplant patients and in 26 related bone marrow donors. Plasma samples from transplant patients were collected immediately after the end of conditioning regimen and up to 270 days after transplant. All plasma samples from transplant patients were negative for KIPyV and WUPyV DNA. Instead, KIPyV DNA was detected in two bone marrow donors. There was no evidence of KIPyV transmission from the donor to the recipient. The data suggest that detection of KIPyV in plasma is sporadic and that KPIyV and WUPyV do not affect the post‐transplant clinical course. However, further studies on a larger sample size and more sensitive PCR methods are needed to confirm these observations. J. Med. Virol. 85: 1122–1124, 2013. © 2013 Wiley Periodicals, Inc.     

Molecular surveillance of rubella viruses in Taiwan from 2005 to 2011

Rubella has been listed as a mandatory notifiable disease in Taiwan since 1988. Because of high coverage rates with an effective vaccine, rubella cases have decreased dramatically in Taiwan since 1994. However, rubella outbreaks still occur due to imported transmission. Five large clusters were detected in Taiwan from 2007 to 2011. In 2007, one cluster was caused by rubella genotype 1E viruses that were imported from Vietnam, whereas another cluster was caused by genotype 2B viruses and was untraceable. In 2008, two clusters were caused by different lineages of genotype 1E viruses that were imported from Malaysia. In 2009, a cluster that was caused by genotype 2B viruses was associated with imported cases from Vietnam. The rubella viruses from 124 confirmed cases from 2005 to 2011 were characterized, and the data revealed that these viruses were distributed in the following four genotypes: 1E (n = 56), 1h (n = 1), 1j (n = 4), and 2B (n = 63). Of these viruses, 93 (75%) were associated with imported cases, and 43 of 56 genotype 1E viruses were associated with imported cases from China, Vietnam, Malaysia, and Indonesia. One genotype 1h virus was imported from Belarus, and three of four genotype 1j viruses were imported from the Philippines. Of 63 rubella genotype 2B viruses, 46 were imported from Vietnam, Thailand, Malaysia, China, Germany, and South Africa. Molecular surveillance allows for the differentiation of circulating rubella viruses and can be used to investigate transmission pathways, which are important to identify the interruption of endemic virus transmission. J. Med. Virol. 85:745–753, 2013. © 2013 Wiley Periodicals, Inc.     

Single nucleotide polymorphisms rs2120131, rs4935047, and rs7095891 in the MBL2 gene show no association with susceptibility to chronic hepatitis B in a Chinese Han population

Thus far, many studies have evaluated the correlation between MBL2 gene polymorphisms and hepatitis B infection. Tag single nucleotide polymorphisms (SNPs) were used to investigate the relationship between MBL2 gene polymorphisms and susceptibility to chronic hepatitis B virus (HBV) infection by comparing 996 chronic HBV infection cases to 301 acute infection controls. There was no significant correlation between rs2120131, rs4935047, and rs7095891 and chronic HBV infection. This suggested that the new SNPs within MBL2 were not associated with susceptibility to chronic hepatitis B in a Chinese Han population. J. Med. Virol. 85:602–607, 2013. © 2013 Wiley Periodicals, Inc.