Danielle E Anderson

• PhD
• Senior Research Fellow at University of Melbourne

Background Crimean‐Congo hemorrhagic fever is a tick‐borne zoonotic disease that may be severe and is present in many African countries. We aimed to understand the seroprevalence and risk for Crimean‐Congo hemorrhagic fever virus in Tanzania by testing archived serum samples from patients enrolled in a prospective cohort study. Methods We prospect...

Background: The COVID-19 pandemic led to the development of many vaccines, most notably the mRNA and recombinant adenoviral vaccines. Whilst the vaccines proved to be effective in preventing severe COVID disease, they failed to prevent infection or to control the ongoing emergence of vaccine escape variant viruses. The rapid waning of vaccine induc...

Measles is a highly infectious disease that continues to spread mainly in developing countries, often resulting in child mortality. Despite the existence of effective vaccines, no specific antivirals are available as targeted therapy to combat measles virus (MeV). The implementation of genome-wide siRNA screens can provide a powerful platform to di...

Despite SARS-CoV-2 vaccines eliciting systemic neutralising antibodies (nAbs), breakthrough infections still regularly occur. Infection helps to generate mucosal immunity, possibly reducing disease transmission. Monitoring mucosal nAbs is predominantly restricted to lab-based assays, which have limited application to the public. In this multi-site...

Zika virus (ZIKV) is a mosquito-borne flavivirus that can vertically transmit from mother to fetus, potentially causing congenital defects, including microcephaly. It is not fully understood why some fetuses experience severe complications after in utero exposure to ZIKV, whereas others do not. Given the antigenic similarity between ZIKV and the cl...

The emergence of novel betacoronaviruses has posed significant financial and human health burdens, necessitating the development of appropriate tools to combat future outbreaks. In this study, we have characterized a human cell line, IGROV-1, as a robust tool to detect, propagate, and titrate betacoronaviruses SARS-CoV-2 and HCoV-OC43. IGROV-1 cell...

While molecular detection has increasingly become the detection method of choice for infectious diseases, antibody detection remains an important approach for diagnosis and surveillance. For henipaviruses, antibody detection methods such as ELISA and Western blot played a key role in the initial discovery of bats as the natural reservoir host. Here...

Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in severely ill patients and the pathophysiology of disease is thought to be immune-mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where they respond to certain viruses and allergens, often promoting inflammation. We observed widespread degran...

The COVID-19 pandemic has sickened millions, cost lives and has devastated the global economy. Various animal models for experimental infection with SARS-CoV-2 have played a key role in many aspects of COVID-19 research. Here, we describe a humanized hACE2 (adenovirus expressing hACE2) NOD-SCID IL2Rγ−/− (NIKO) mouse model and compare infection with...

The COVID-19 pandemic has sickened millions, cost lives and has devastated the global economy. Various animal models for experimental infection with SARS-CoV-2 have played a key role in many aspects of COVID-19 research. Here, we describe a humanized AdV-hACE2 NOD-SCID IL2Rγ-/- (NIKO) mouse model and compared infection with ancestral and mutant (SA...

The importance of genomic surveillance on emerging diseases continues to be highlighted with the ongoing SARS-CoV-2 pandemic. Here, we present an analysis of a new bat-borne mumps virus (MuV) in a captive colony of lesser dawn bats (Eonycteris spelaea). This report describes an investigation of MuV-specific data originally collected as part of a lo...

Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation and infective exacerbations, however, in-vitro model systems for the study of host-pathogen interaction at the individual level are lacking. Here, we describe the establishment of nasopharyngeal and bronchial organoids from healthy individuals and COPD that recapitu...

The ongoing COVID-19 pandemic has demonstrated that viral diseases represent an enormous public health and economic threat to mankind and that individuals with compromised immune systems are at greater risk of complications and death from viral diseases. The development of broad-spectrum antivirals is an important part of pandemic preparedness. Her...

Bats are reservoir hosts of many zoonotic viruses with pandemic potential. We utilized single-cell transcriptome sequencing (scRNA-seq) to analyze the immune response in bat lungs upon in vivo infection with a double-stranded RNA virus, Pteropine orthoreovirus PRV3M. Bat neutrophils were distinguished by high basal IDO1 expression. NK cells and T c...

Bats have been recognized as an exceptional viral reservoir, especially for coronaviruses. At least three bat zoonotic coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2) have been shown to cause severe diseases in humans and it is expected more will emerge. One of the major features of CoVs is that they are all highly prone to recombination. An extr...

Bats have been recognized as an exceptional viral reservoir, especially for coronaviruses. At least three bat zoonotic coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2) have been shown to cause severe diseases in humans and it is expected more will emerge. One of the major features of CoVs is that they are all highly prone to recombination. An extr...

Background Comprehensive characterization of exposures and immune responses to viral infections is critical to a basic understanding of human health and disease. We previously developed the VirScan system, a programmable phage-display technology for profiling antibody binding to a library of peptides designed to span the human virome. Previous VirS...

Background Hendra virus (HeV) has caused lethal disease outbreaks in humans and horses in Australia. Flying foxes are the wildlife reservoir from which the virus was first isolated in 1996. Following a heat stress mortality event in Australian flying foxes in 2013, a novel HeV variant was discovered. This study describes the subsequent surveillance...

Multiple successful vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to address the ongoing coronavirus disease 2019 (Covid-19) pandemic. In the present work, we describe a subunit vaccine based on the SARS-CoV-2 spike protein coadministered with CpG adjuvant. To enhance the immunogenicity of our for...

Significance We established a genome-wide CRISPR library and a genome-wide RNA interference library for a bat species and performed two genetic screens to uncover host factors of bat cells involved in virus infections. Although the viruses and methodologies used were different in the two screens, we identified one common protein, MTHFD1, as a broad...

Measles virus (MeV) is a highly contagious pathogen that enters the human host via the respiratory route. Besides acute pathologies including fever, cough and the characteristic measles rash, the infection of lymphocytes leads to substantial immunosuppression that can exacerbate the outcome of infections with additional pathogens. Despite the avail...

SARS-CoV-2 is a major threat to global health. Here, we investigate the RNA structure and RNA-RNA interactions of wildtype (WT) and a mutant (Δ382) SARS-CoV-2 in cells using Illumina and Nanopore platforms. We identify twelve potentially functional structural elements within the SARS-CoV-2 genome, observe that subgenomic RNAs can form different str...

Outbreak analysis and transmission surveillance of viruses can be performed via whole-genome sequencing after viral isolation. Such techniques have recently been applied to characterize and monitor SARS-CoV-2, the etiological agent of the COVID-19 pandemic. However, the isolation and culture of SARS-CoV-2 is time consuming and requires biosafety le...

Bats have been increasingly recognised as an exceptional reservoir for emerging zoonotic viruses for the past few decades. Recent studies indicate that the unique bat immune system may be partially responsible for their ability to co-exist with viruses with minimal or no clinical diseases. In this review, we discuss the history and importance of ba...

We tested pre-pandemic (2015-2019) plasma samples from 148 Vietnamese children, and 100 Vietnamese adults at high risk of zoonotic infections, for antibodies against SARS-CoV-2 nucleocapsid and spike proteins. None was positive. The data thus demonstrated that there was no evidence of prior serological cross-reactivity with SARS-CoV-2 that might ex...

We tested pre-pandemic (2015-2019) plasma samples from 148 Vietnamese children, and 100 Vietnamese adults at high risk of zoonotic infections, for antibodies against SARS-CoV-2 nucleocapsid and spike proteins. None was positive, indicating no prior serological cross-reactivity with SARS-CoV-2 that might explain the low numbers of COVID-19 in Vietna...

Zika virus (ZIKV) is an emerging arbovirus with recent global expansion. Historically, ZIKV infections with Asian lineages have been associated with mild disease such as rash and fever. However, recent Asian sub-lineages have caused outbreaks in the South Pacific and Latin America with increased prevalence of neurological disorders in infants and a...

Background Hendra virus (HeV) has caused lethal disease outbreaks in humans and horses in Australia. Pteropid bats (flying foxes) are the wildlife reservoir from which the virus was first isolated in 1996. Following a heat stress mortality event in Australian flying foxes in 2013, a novel HeV variant was discovered. This study describes the subsequ...

Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in severely ill patients and the pathophysiology of disease is thought to be immune-mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where they respond to certain viruses and allergens, often promoting inflammation. We observed widespread degran...

An accurate depiction of the convalescent COVID-19 immunome will help delineate the immunological milieu crucial for disease resolution and protection. Using mass cytometry, we characterized the immune architecture in patients recovering from mild COVID-19. We identified a virus-specific immune rheostat composed of an effector T (Teff) cell recall...

Background Host determinants of severe coronavirus disease 2019 include advanced age, comorbidities and male sex. Virologic factors may also be important in determining clinical outcome and transmission rates, but limited patient-level data is available. Methods We conducted an observational cohort study at seven public hospitals in Singapore. Cli...

SARS-CoV-2 has emerged as a major threat to global public health, resulting in global societal and economic disruptions. Here, we investigate the intramolecular and intermolecular RNA interactions of wildtype (WT) and a mutant (Δ382) SARS-CoV-2 virus in cells using high throughput structure probing on Illumina and Nanopore platforms. We identified...

Antibody response against nucleocapsid and spike proteins of SARS-CoV-2 in 11 persons with mild or asymptomatic infection rapidly increased after infection. At weeks 18-30 after diagnosis, all remained seropositive but spike protein-targeting antibody titers declined. These data may be useful for vaccine development.

Multiple successful vaccines against SARS-CoV-2 are urgently needed to address the ongoing Covid-19 pandemic. In the present work, we describe a subunit vaccine based on the SARS-CoV-2 spike protein co-administered with CpG adjuvant. To enhance the immunogenicity of our formulation, both antigen and adjuvant were encapsulated with our proprietary a...

There have been several major outbreaks of emerging viral diseases, including Hendra, Nipah, Marburg and Ebola virus diseases, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS)—as well as the current pandemic of coronavirus disease 2019 (COVID-19). Notably, all of these outbreaks have been linked to suspected zoon...

SARS-CoV-2 has emerged as a major threat to global public health, resulting in global societal and economic disruptions. Here, we investigate the intramolecular and intermolecular RNA interactions of wildtype (WT) and a mutant (Δ382) SARS-CoV-2 virus in cells using high throughput structure probing on Illumina and Nanopore platforms. We identified...

The novel coronavirus SARS-CoV-2 is the causative agent of Coronavirus Disease 2019 (COVID-19), a global healthcare and economic catastrophe. Understanding of the host immune response to SARS-CoV-2 is still in its infancy. A 382-nt deletion strain lacking ORF8 (Δ382 herein) was isolated in Singapore in March 2020. Infection with Δ382 was associated...

Despite initial findings indicating that SARS-CoV and SARS-CoV-2 are genetically related belonging to the same virus species and that the two viruses used the same entry receptor, angiotensin-converting enzyme 2 (ACE2), our data demonstrated that there is no detectable cross-neutralization by SARS patient sera against SARS-CoV-2. We also found that...

Introduction: Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant...

Purpose: To report bilateral follicular conjunctivitis in two confirmed Coronavirus (COVID-19) patients with the presence of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) in conjunctival swab specimens. Participants and methods: Two unrelated patients with confirmed SARS-CoV-2 infection and bilateral acute conjunctivitis were exam...

A robust serological test to detect neutralizing antibodies to SARS-CoV-2 is urgently needed to determine not only the infection rate, herd immunity and predicted humoral protection, but also vaccine efficacy during clinical trials and after large-scale vaccination. The current gold standard is the conventional virus neutralization test requiring l...

Background: Key knowledge gaps remain in the understanding of viral dynamics and immune response of SARS-CoV-2 infection. Methods: We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age 46 years, 56%...

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with a 382-nucleotide deletion (∆382) in the open reading frame 8 (ORF8) region of the genome have been detected in Singapore and other countries. We investigated the effect of this deletion on the clinical features of infection. Methods We retrospectively identified...

During the SARS epidemic in 2003/2004, a number of deletions were observed in ORF8 of SARS-CoV, and eventually deletion variants became predominant, leading to the hypothesis that ORF8 was an evolutionary hot spot for adaptation of SARS-CoV to humans. However, due to the successful control of the SARS epidemic, the importance of these deletions for...

IntroductionAs of 22 June 2020, Severe Acute Respiratory Syndrome (SARS)-coronavirus (CoV)-2 has infected more than 8.95 million people worldwide, causing > 468,000 deaths. The virus is transmitted through respiratory droplets and physical contact from contaminated surfaces to the mucosa. Hand hygiene and oral decontamination among other measures a...

The neuraminidase (NA) inhibitor (NAI) oseltamivir (OST) is the most widely used influenza antiviral drug. Several NA amino acid substitutions are reported to reduce viral susceptibility to OST in in vitro assays. However, whether there is a correlation between the level of reduction in susceptibility in vitro and the efficacy of OST against these...

In response to the coronavirus disease 2019 (COVID-19) outbreak, caused by the SARS-CoV-2 virus, multiple diagnostic tests are required globally for acute disease diagnosis, contact tracing, monitoring of asymptomatic infection rates and assessing herd immunity. While PCR remains the frontline test of choice in the acute diagnostic setting, serolog...

Introduction: Within six months of its emergence, SARS‑CoV‑2 has infected 5.5 million people worldwide, causing >345,000 deaths. The virus is transmitted through respiratory droplets and physical contact from contaminated surfaces to the mucosa. Hand hygiene and oral decontamination among other measures are key to preventing the spread of the virus...

Introduction: Within six months of its emergence, SARS‑CoV‑2 has infected 5.5 million people worldwide, causing >345,000 deaths. The virus is transmitted through respiratory droplets and physical contact from contaminated surfaces to the mucosa. Hand hygiene and oral decontamination among other measures are key to preventing the spread of the virus...

Rousettus bat coronavirus GCCDC1 (RoBat-CoV GCCDC1) is a cross-family recombinant coronavirus that has previously only been reported in wild-caught bats in Yúnnan, China. We report the persistence of a related strain in a captive colony of lesser dawn bats captured in Singapore. Genomic evidence of the virus was detected using targeted enrichment s...

At this critical moment of the international response to the COVID-19 outbreak, there is an urgent need for a robust serological test to detect neutralizing antibodies to SARS-CoV-2. Such a test is not only important for contact tracing, but for determining infection rate, herd immunity and predicted humoral protection. The current gold standard is...

Background Elucidation of the chain of disease transmission and identification of the source of coronavirus disease 2019 (COVID-19) infections are crucial for effective disease containment. We describe an epidemiological investigation that, with use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays, established link...

Bats are responsible for the zoonotic transmission of several major viral diseases including the 2003 SARS outbreak and the ongoing COVID-19 pandemic. While bat genomic sequencing studies have revealed characteristic adaptations of the innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dis...

To date, the SARS-CoV-2 genome has been considered genetically more stable than SARS-CoV or MERS-CoV. Here we report a 382-nt deletion covering almost the entire open reading frame 8 (ORF8) of SARS-CoV-2 obtained from eight hospitalized patients in Singapore. The deletion also removes the ORF8 transcription-regulatory sequence (TRS), which in turn...

Importance Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has spread globally with sustained human-to-human transmission outside China. Objective To report the initial experience in Singapore with the epidemiologic investigation of this outbreak, clinical features, and management. Design...

Ocular transmission of COVID-19 is uncertain. 64 tear samples were collected from 17 COVID-19 patients between Day 3 to Day 20 from initial symptoms. Neither viral culture nor reverse transcription polymerase chain reaction (RT-PCR) detected the virus, suggesting a low risk of ocular transmission.

Coronaviruses (CoVs) of bat origin have caused two pandemics in this century. Severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV both originated from bats, and it is highly likely that bat coronaviruses will cause future outbreaks. Active surveillance is both urgent and essential to predict and mitigate the...

Henipaviruses form a genus of RNA viruses in the family Paramyxoviridae, order Mononegavirales. The key members of the genus, Hendra and Nipah viruses, have been associated with multiple lethal disease outbreaks in humans and animals. Bats are the main reservoir of henipaviruses and there are molecular and serological evidences to suggest that heni...

Dromedary camels are important reservoir hosts of various coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV) that cause human infections. CoV genomes regularly undergo recombination during infection as observed in bat SARS-related CoVs. Here we report for the first time that only a small proportion of MERS-CoV receptor...

Bats are important reservoirs and vectors in the transmission of emerging infectious diseases. Many highly pathogenic viruses such as SARS-CoV and rabies-related lyssaviruses have crossed species barriers to infect humans and other animals. In this study we monitored the major roost sites of bats in Singapore, and performed surveillance for zoonoti...

Next-generation sequencing (NGS) techniques offer an unprecedented "step-change" increase in the quantity and quality of sequence data rapidly generated from a sample and can be applied to obtain ultra-deep coverage of viral genomes. This is not possible with the routinely used Sanger sequencing method that gives the consensus reads, or by cloning...

The high genetic variability of influenza A viruses poses a continual challenge to seasonal and pandemic vaccine development, leaving antiviral drugs as the first line of defense against antigenically different strains or new subtypes. As resistance against drugs targeting viral proteins emerges rapidly, we assessed the antiviral activity of alread...

Pteropine orthoreoviruses (PRV) are emerging bat-borne viruses with proven zoonotic transmission. We recently demonstrated human exposure to PRV in Singapore, which together with previous reports from Malaysia and Vietnam suggest that human infection of PRV may occur periodically in the region. This raises the question whether bats are the only sou...

Paramyxoviruses and pneumoviruses have similar life cycles and share the respiratory tract as a point of entry. In comparative genome-scale siRNA screens with wild-type-derived measles, mumps, and respiratory syncytial viruses in A549 cells, a human lung adenocarcinoma cell line, we identified vesicular transport, RNA processing pathways, and trans...

The frequency of epidemics caused by Dengue viruses 1–4, Zika virus and Chikungunya viruses have been on an upward trend in recent years driven primarily by uncontrolled urbanization, mobility of human populations and geographical spread of their shared vectors, Aedes aegypti and Aedes albopictus. Infections by these viruses present with similar cl...

In order to ascertain if the other properties of the bait affected the affinity of the baits and fragments, we performed a principle component analysis (PCA) with the baits’ GC content, melting temperature (Tm), Gibbs free energy, sequence identity between bait and genome, and bait pull down efficiency measured by mean genome coverage. The samples...

Genomic sequences extracted from NCBI used to design baits. (XLSX)

Properties of baits used in the experiments. (XLSX)

Sequencing information in detail for unenriched and enriched experiment (Fig 1), the ZIKV dilution series experiment (Fig 2) and a DENV2 dilution series experiment (Figure not shown). (XLSX)

Genome coverage plots of unenriched and enriched samples of DENV2, DENV3 and DENV4. The top panel (A, C, E) are unenriched samples whereas the bottom panel (B, D, F) are matched enriched samples with baits. From the outermost circle, each plot reads as the viral genes in the genome, SNPs (single nucleotide polymorphisms) detected, depth of coverage...

The mean genomic coverage of the clinical samples enriched by the DENV, CHIKV and ZIKV baits panel: A) 143 DENV1 samples, B) 27 DENV4 samples and C) 162 ZIKV samples. The standard error is represented as a lighter shade around the mean at each genomic location. (TIF)

Stacked depth of coverage at regions were the baits hybridize with the genome. The enriched samples used in Fig 2 (consisting of DENV1, 2, 3 and 4, CHIKV and ZIKV) was used to group the baits and genome targets based on their nucleotide identity: A) >95% identity (n = 111), B) 90–95% identity (n = 32), C) 85–90% identity (n = 10) and D) 80–85% iden...

Effect of library size on genome enrichment by the baits panel. The x-axis is the mean library size of the samples and y-axis represents the genome coverage distribution given by 1-SD (standard deviation) of the sequencing reads distribution enriched around the bait. The range of library sizes for DENV1, DENV4, and ZIKV cohort samples are between 8...

Enrichment protocol used in experiments. (DOCX)

In the version of this Letter originally published, in the ‘Phylogenetic analysis’ section of the Methods, the authors mistakenly stated that the GenBank accession number for the Ravn virus genome sequence was FJ750958. The correct accession number is DQ447649 for Ravn virus, Kenya, 1987. Accordingly, the label ‘RAVN2007’ in Fig. 1b should have bee...

The acknowledgement section in the original article was published incorrectly.

Bats are special in their ability to host emerging viruses. As the only flying mammal, bats endure high metabolic rates yet exhibit elongated lifespans. It is currently unclear whether these unique features are interlinked. The important inflammasome sensor, NLR family pyrin domain containing 3 (NLRP3), has been linked to both viral-induced and age...

In the last two decades, several high impact zoonotic disease outbreaks have been linked to bat-borne viruses. These include SARS coronavirus, Hendra virus and Nipah virus. In addition, it has been suspected that ebolaviruses and MERS coronavirus are also linked to bats. It is being increasingly accepted that bats are potential reservoirs of a larg...

Filoviruses, especially Ebola virus (EBOV) and Marburg virus (MARV), are notoriously pathogenic and capable of causing severe haemorrhagic fever diseases in humans with high lethality1,2. The risk of future outbreaks is exacerbated by the discovery of other bat-borne filoviruses of wide genetic diversity globally3–5. Here we report the characteriza...

Despite molecular and serologic evidence of Nipah virus in bats from various locations, attempts to isolate live virus have been largely unsuccessful. We report isolation and full-genome characterization of 10 Nipah virus isolates from Pteropus medius bats sampled in Bangladesh during 2013 and 2014.