Reactivation of a Vaccine Escape Hepatitis B Virus Mutant in a Cambodian Patient During Anti-Hepatitis C Virus Therapy.

A 76-year-old Cambodian man co-infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) 6c-1 presented for care. HBV DNA was intermittently detectable despite anti-HBs levels being above the protective threshold. During treatment for HCV, HBV DNA levels increased. Sequencing revealed multiple mutations including vaccine escape mutation and mutations predicted to enhance fitness. This case represents exacerbation of an HBV vaccine escape mutant during a direct-acting antiviral therapy.

Hepatitis B virus outreach to immigrant population in Greater Boston Area: Key to improving hepatitis B knowledge.

AIM: To characterize the understanding of hepatitis B virus (HBV) and determine if outreach improves HBV understanding among Greater Boston Area immigrants. METHODS: Six outreach sessions were held in various community venues in the Greater Boston Area. Verbal consent was obtained from participants prior to starting each session. Each session included a pre-session questionnaire, followed by a teaching session, and then a post-session questionnaire. In person interpreters were present for translation during the teaching session and assistance for questionnaire completion when needed. The questions were developed based on the HBV clinical experience of physicians who serve largely immigrant populations. Questionnaires included Likert-type scale, open-ended, and true-false questions. All results were anonymous. RESULTS: One hundred and one people participated in this study. Participants were 30% male with ages ranging from 19 to 87 years. The study population included immigrants from 21 countries, as well as seven United States-born participants. The greatest numbers of participants were from Somalia (44%), Morocco (10%), and Cameroon (8%). Pre session questionnaires revealed that 42% of participants were unaware that HBV can cause cancer, and 50% were unaware that therapies for HBV exist. Our brief teaching intervention led to improved scores on post session questionnaires. For example, at baseline, 58% of participants responded correctly to the question "HBV infection can cause scarring of the liver and liver cancer", whereas 79% of participants responded correctly after the teaching session (P = 0.01). Furthermore, the mean of total correct answers in the true or false portion of the questionnaire increased from 5.5 to 7.6 (P < 0.001). CONCLUSION: A teaching session targeting Boston Immigrants at-risk for HBV helped improve scores on HBV knowledge questionnaires. Outreach may empower at-risk patients to pro-actively seek HBV care.

HELZ2 Is an IFN Effector Mediating Suppression of Dengue Virus.

Flaviviral infections including dengue virus are an increasing clinical problem worldwide. Dengue infection triggers host production of the type 1 IFN, IFN alpha, one of the strongest and broadest acting antivirals known. However, dengue virus subverts host IFN signaling at early steps of IFN signal transduction. This subversion allows unbridled viral replication which subsequently triggers ongoing production of IFN which, again, is subverted. Identification of downstream IFN antiviral effectors will provide targets which could be activated to restore broad acting antiviral activity, stopping the signal to produce endogenous IFN at toxic levels. To this end, we performed a targeted functional genomic screen for IFN antiviral effector genes (IEGs), identifying 56 IEGs required for antiviral effects of IFN against fully infectious dengue virus. Dengue IEGs were enriched for genes encoding nuclear receptor interacting proteins, including HELZ2, MAP2K4, SLC27A2, HSP90AA1, and HSP90AB1. We focused on HELZ2 (Helicase With Zinc Finger 2), an IFN stimulated gene and IEG which encodes a promiscuous nuclear factor coactivator that exists in two isoforms. The two unique HELZ2 isoforms are both IFN responsive, contain ISRE elements, and gene products increase in the nucleus upon IFN stimulation. Chromatin immunoprecipitation-sequencing revealed that the HELZ2 complex interacts with triglyceride-regulator LMF1. Mass spectrometry revealed that HELZ2 knockdown cells are depleted of triglyceride subsets. We thus sought to determine whether HELZ2 interacts with a nuclear receptor known to regulate immune response and lipid metabolism, AHR, and identified HELZ2:AHR interactions via co-immunoprecipitation, found that AHR is a dengue IEG, and that an AHR ligand, FICZ, exhibits anti-dengue activity. Primary bone marrow derived macrophages from HELZ2 knockout mice, compared to wild type controls, exhibit enhanced dengue infectivity. Overall, these findings reveal that IFN antiviral response is mediated by HELZ2 transcriptional upregulation, enrichment of HELZ2 protein levels in the nucleus, and activation of a transcriptional program that appears to modulate intracellular lipid state. IEGs identified in this study may serve as both (1) potential targets for host directed antiviral design, downstream of the common flaviviral subversion point, as well as (2) possible biomarkers, whose variation, natural, or iatrogenic, could affect host response to viral infections.