Climate Variability and Ross River Virus Transmission in Townsville Region, Australia 1985 to 1996

Background How climate variability affects the transmission of infectious diseases at a regional level remains unclear. In this paper, we assessed the impact of climate variation on the Ross River virus (RRv) transmission in the Townsville region, Queensland, north-east Australia. Methods Population-based information was obtained on monthly variations in RRv cases, climatic factors, sea level, and population growth between 1985 and 1996. Cross-correlations were computed for a series of associations between climate variables (rainfall, maximum temperature, minimum temperature, relative humidity and high tide) and the monthly incidence of RRv disease over a range of time lags. The impact of climate variability on RRv transmission was assessed using the seasonal auto-regressive integrated moving average (SARIMA) model. Results There were significant correlations of the monthly incidence of RRv to rainfall, maximum temperature, minimum temperature and relative humidity, all at a lag of 2 months, and high tide in the current month. The results of SARIMA models show that monthly average rainfall (β=0.0012, p=0.04) and high tide (β=0.0262, p=0.01) were significantly associated with RRv transmission, although temperature and relative humidity did not seem to have played an important role in the Townsville region. Conclusions Rainfall, and high tide were likely to be key determinants of RRv transmission in the Townsville region

Identification of a Cryptic Prokaryotic Promoter within the cDNA Encoding the 5′ End of Dengue Virus RNA Genome

Infectious cDNA clones of RNA viruses are important research tools, but flavivirus cDNA clones have proven difficult to assemble and propagate in bacteria. This has been attributed to genetic instability and/or host cell toxicity, however the mechanism leading to these difficulties has not been fully elucidated. Here we identify and characterize an efficient cryptic bacterial promoter in the cDNA encoding the dengue virus (DENV) 5′ UTR. Following cryptic transcription in E. coli, protein expression initiated at a conserved in-frame AUG that is downstream from the authentic DENV initiation codon, yielding a DENV polyprotein fragment that was truncated at the N-terminus. A more complete understanding of constitutive viral protein expression in E. coli might help explain the cloning and propagation difficulties generally observed with flavivirus cDNA

Autonomous Targeting of Infectious Superspreaders Using Engineered Transmissible Therapies

Infectious disease treatments, both pharmaceutical and vaccine, face three universal challenges: the difficulty of targeting treatments to high-risk ‘superspreader’ populations who drive the great majority of disease spread, behavioral barriers in the host population (such as poor compliance and risk disinhibition), and the evolution of pathogen resistance. Here, we describe a proposed intervention that would overcome these challenges by capitalizing upon Therapeutic Interfering Particles (TIPs) that are engineered to replicate conditionally in the presence of the pathogen and spread between individuals — analogous to ‘transmissible immunization’ that occurs with live-attenuated vaccines (but without the potential for reversion to virulence). Building on analyses of HIV field data from sub-Saharan Africa, we construct a multi-scale model, beginning at the single-cell level, to predict the effect of TIPs on individual patient viral loads and ultimately population-level disease prevalence. Our results show that a TIP, engineered with properties based on a recent HIV gene-therapy trial, could stably lower HIV/AIDS prevalence by ∼30-fold within 50 years and could complement current therapies. In contrast, optimistic antiretroviral therapy or vaccination campaigns alone could only lower HIV/AIDS prevalence by <2-fold over 50 years. The TIP's efficacy arises from its exploitation of the same risk factors as the pathogen, allowing it to autonomously penetrate superspreader populations, maintain efficacy despite behavioral disinhibition, and limit viral resistance. While demonstrated here for HIV, the TIP concept could apply broadly to many viral infectious diseases and would represent a new paradigm for disease control, away from pathogen eradication but toward robust disease suppression

Unconventional Repertoire Profile Is Imprinted during Acute Chikungunya Infection for Natural Killer Cells Polarization toward Cytotoxicity

Chikungunya virus (CHIKV) is a worldwide emerging pathogen. In humans it causes a syndrome characterized by high fever, polyarthritis, and in some cases lethal encephalitis. Growing evidence indicates that the innate immune response plays a role in controlling CHIKV infection. We show here that CHIKV induces major but transient modifications in NK-cell phenotype and function soon after the onset of acute infection. We report a transient clonal expansion of NK cells that coexpress CD94/NKG2C and inhibitory receptors for HLA-C1 alleles and are correlated with the viral load. Functional tests reveal cytolytic capacity driven by NK cells in the absence of exogenous signals and severely impaired IFN-γ production. Collectively these data provide insight into the role of this unique subset of NK cells in controlling CHIKV infection by subset-specific expansion in response to acute infection, followed by a contraction phase after viral clearance

The Molecular Epidemiology and Evolution of Murray Valley Encephalitis Virus: Recent Emergence of Distinct Sub-lineages of the Dominant Genotype 1

© 2015 Williams et al. Background: Recent increased activity of the mosquito-borne Murray Valley encephalitis virus (MVEV) in Australia has renewed concerns regarding its potential to spread and cause disease. Methodology/Principal Findings: To better understand the genetic relationships between earlier and more recent circulating strains, patterns of virus movement, as well as the molecular basis of MVEV evolution, complete pre-membrane (prM) and Envelope (Env) genes were sequenced from sixty-six MVEV strains from different regions of the Australasian region, isolated over a sixty year period (1951–2011). Phylogenetic analyses indicated that, of the four recognized genotypes, only G1 and G2 are contemporary. G1 viruses were dominant over the sampling period and found across the known geographic range of MVEV. Two distinct sub-lineages of G1 were observed (1A and 1B). Although G1B strains have been isolated from across mainland Australia, Australian G1A strains have not been detected outside northwest Australia. Similarly, G2 is comprised of only Western Australian isolates from mosquitoes, suggesting G1B and G2 viruses have geographic or ecological restrictions. No evidence of recombination was found and a single amino acid substitution in the Env protein (S332G) was found to be under positive selection, while several others were found to be under directional evolution. Evolutionary analyses indicated that extant genotypes of MVEV began to diverge from a common ancestor approximately 200 years ago. G2 was the first genotype to diverge, followed by G3 and G4, and finally G1, from which subtypes G1A and G1B diverged between 1964 and 1994. Conclusions/Significance: The results of this study provides new insights into the genetic diversity and evolution of MVEV. The demonstration of co-circulation of all contemporary genetic lineages of MVEV in northwestern Australia, supports the contention that this region is the enzootic focus for this virus

Analysis of a recombinant dengue-2 virus dengue-3 virus hybrid envelope protein expressed in a secretory baculovirus system

In a step towards a tetravalent dengue virus subunit vaccine which is economical to produce, highly immunogenic and stable, a hybrid dengue virus envelope (E) protein molecule has been constructed, It consists of 36 amino acids from the membrane protein, the N-terminal 288 amino acids of the dengue-2 virus E protein plus amino acids 289-424 of the dengue-3 virus E protein, It has been engineered for secretory expression by fusion to a mellitin secretory signal sequence and truncation of the hydrophobic transmembrane segment, Using the baculovirus expression system and serum-free conditions, more than 95% of recombinant dengue-2 virus-dengue-3 virus hybrid E protein (rD2D3E) was secreted into the cell culture supernatant in a stable form with multiple features indicative of preserved conformation, The hybrid molecule reacted with a panel of dengue virus-and flavivirus-specific MAbs which recognize linear or conformational epitopes on dengue virions, Human dengue virus-specific antisera also reacted with the protein, The hybrid rD2D3E protein was able to inhibit the in vitro binding of dengue-2 and dengue-3 viruses to human myelomonocytic cells, suggesting that the receptor-binding epitope(s) was preserved, Adjuvant-free immunization with the hybrid protein induced an antibody response to both dengue-2 and dengue-3 virus in outbred mice, comparable in strength to that of individual rD2E and rD3E proteins. Notably, these antibody responses were primarily of the IgG2a and IgG2b isotype. A strong dengue virus cross-reactive T cell response was also induced in the mice, suggesting that dengue virus hybrid E proteins could form the basis of an efficacious multivalent dengue virus vaccine

Neglected Australian arboviruses associated with undiagnosed undifferentiated febrile illness

Australia is home to over 75 arthropod-borne viruses, with least 13 associated with human infection. Ross River (RRV), Barmah Forest (BFV), Murray Valley encephalitis (MVEV) and Kunjin (KUNV) viruses commonly cause disease and are diagnosed in pathology laboratories. Following commercial ELISA development to diagnose RRV, in 2016 cases exceeded 9,000. However, other indigenous arboviruses, such as Alfuy (ALFV), Edge Hill (EHV), Kokobera (KOKV), Sindbis (SINV) and Stratford (STRV), are not routinely tested. Little is known of their role in human pathology, undifferentiated febrile illness (UFI) or serious diseases. This study aimed to determine prevalence of infection of humans with these neglected Australian arboviruses and whether any causes UFI. Screening of 1,000 age- and gender-stratified plasma samples from healthy Queensland-resident blood donors for antiviral IgG antibodies by indirect ELISA produced non-specific reactivity so a sub-sample was tested by plaque reduction neutralisation. 492 acute-phase samples from UFI patients in northern Australia were also screened by indirect immunofluorescence for virus-specific IgM antibodies. There was a linear increase in prevalence of neutralising antibodies with annual seroconversion rates ranging from RRV 1.3% to KOKV and STRV 0.05%. Among UFI patient samples 5.2% contained IgM against one or more of: RRV 0.8%; BFV 0.4%; ALF 1.4%; EHV 1.8%; KOKV 1.4%; KUNV 2.4%; MVEV 1.0%; STRV 1.2%. No age-dependent anti-ALFV antibodies prevalence was observed. A small proportion of UFI was attributable to infection; 2 ALFV, 4 EHV, 14 KOKV, 8 KUNV, 8 MVEV and 1 STRV identified cases per 1000 persons tested. These results indicate several neglected Australian arboviruses have been infecting humans for decades and some may be associated with UFI. A program of systematic testing of UFI patients is recommended to examine for recent infection to determine the significance of the burden of the disease that these neglected arboviruses cause

Neglected Australian arboviruses and undifferentiated febrile illness: Addressing public health challenges arising from the ‘Developing Northern Australia’ government policy

The Australian Government is currently promoting the development of Northern Australia, with an associated increase in the local population. Consequent to this is the public health threat posed by heightened human exposure to many previously neglected arboviruses that are indigenous to the region. This initiative to support economic activity in the tropical north of the continent is leading to the accelerated expansion of an infection-naïve human population into hitherto un-encountered ecosystems inhabited by reservoir animals and vectors for these arboviruses. Combined with an apparent rise in the number and impact of dramatic climate events, such as tropical cyclones and floods caused by torrential monsoonal rainfall, this heightens the potential for viral transmission to humans. More than 75 arboviruses have been identified in Australia, some of which are associated with human disease but for which routine tests are not available to diagnose infection. Here, we describe briefly the neglected Australian arboviruses that are most likely to emerge as significant agents of human disease in the coming decades. We also advocate the establishment of a thorough surveillance and diagnostic protocol, including developing new pan-viral rapid tests for primary care use to assist in the early diagnosis and correct treatment of affected patients. We propose that the implementation of these activities will enhance our understanding of the geographical range, prevalence, identification and control of neglected Australian arboviruses. This would minimise and limit the possibility of large-scale outbreaks with these agents as population and economic growth expands further into Australia’s tropical north

Neglected Australian arboviruses: Quam gravis?

At least 75 arboviruses have been identified from Australia. Most have a zoonotic transmission cycle, maintained in the environment by cycling between arthropod vectors and susceptible mammalian or avian hosts. The primary arboviruses that cause human disease in Australia are Ross River, Barmah Forest, Murray Valley encephalitis, Kunjin and dengue. Several other arboviruses are associated with human disease but little is known about their clinical course and diagnostic testing is not routinely available. Given the significant prevalence of undifferentiated febrile illness in Australia, investigation of the potential threat to public health presented by these viruses is required. © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved