Saravanan Thangamani

• MSc., PhD.
• Professor at SUNY Upstate Medical University

Introduction COVID-19 remains a significant threat to public health globally. Infection in some susceptible individuals causes life-threatening acute lung injury (ALI/ARDS) and/or death. Human surfactant protein A (SP-A) is a C-type lectin expressed in the lung and other mucosal tissues, and it plays a critical role in host defense against various...

Introduction Powassan virus (POWV), a vector-borne pathogen transmitted by Ixodes ticks in North America, is the causative agent of Powassan encephalitis. As obligate hematophagous organisms, ticks transmit pathogens like POWV at the tick bite site, specifically during the initial stages of feeding. Tick feeding and salivary factors modulate the ho...

Eilat (EILV)/chikungunya virus (CHIKV), an insect-based chimeric alphavirus was previously reported to protect mice months after a single dose vaccination. The underlying mechanisms of host protection are not clearly defined. Here, we assessed the capacity of EILV/CHIKV to induce quick and durable protection in cynomolgus macaques. Both EILV/CHIKV...

COVID-19 remains a significant threat to public health globally. Infection in some susceptible individuals causes life-threatening acute lung injury (ALI/ARDS) and/or death. Human surfactant protein A (SP-A) is a C-type lectin expressed in the lung and other mucosal tissues, and it plays a critical role in host defense against various pathogens. Th...

The Aedes aegypti mosquito is a vector of many infectious agents, including flaviviruses such as Zika virus. Components of mosquito saliva have pleomorphic effects on the vertebrate host to enhance blood feeding, and these changes also create a favorable niche for pathogen replication and dissemination. Here, we demonstrate that human CD47, which i...

Author Summary The Powassan virus causes a nationally notifiable disease which can cause severe neurological disease in humans owing to the lack of approved vaccines or therapeutics. Although two distinct lineages circulate in North America, clinical differentiation does not typically occur because pathology has been assumed to be similar between l...

Chikungunya virus (CHIKV), which induces chikungunya fever and chronic arthralgia, is an emerging public health concern. Safe and efficient vaccination strategies are needed to prevent or mitigate virus-associated acute and chronic morbidities for preparation of future outbreaks. Eilat (EILV)/CHIKV, a chimeric alphavirus which contains the structur...

Introduction SARS coronavirus 2 (SARS-CoV-2) infects human angiotensin-converting enzyme 2 (hACE2)-expressing lung epithelial cells through its spike (S) protein. The S protein is highly glycosylated and could be a target for lectins. Surfactant protein A (SP-A) is a collagen-containing C-type lectin, expressed by mucosal epithelial cells and media...

Heartland virus was first isolated in 2009 from two patients in Missouri and is transmitted by the Lone Star tick, Amblyomma americanum. To understand disease transmission and pathogenesis, it is necessary to develop an animal model which utilizes the natural route of transmission and manifests in a manner similar to documented human cases. Herein...

Tick-borne flaviviruses (TBFV) can cause severe neuroinvasive disease which may result in death or long-term neurological deficit in over 50% of survivors. Multiple mechanisms for invasion of the central nervous system (CNS) by flaviviruses have been proposed including axonal transport, transcytosis, endothelial infection, and Trojan horse routes....

The COVID‐19 pandemic severely affected the medical education worldwide. The infection risk for medical students and healthcare personnel who work with COVID‐19 positive cadavers or tissues remains unclear. Moreover, COVID‐19 positive cadavers have been rejected by medical schools, adversely impacting the continuum of medical education. Herein, the...

Heartland virus was first isolated in 2009 from two patients in Missouri and is transmitted by the lone star tick, Amblyomma americanum. To understand disease transmission and pathogenesis, it is necessary to develop an animal model that utilizes the natural transmission route and manifests in a manner similar to documented human cases. Herein we d...

SARS coronavirus 2 (SARS-CoV-2) infects human angiotensin-converting enzyme 2 (hACE2)-expressing lung epithelial cells through its spike (S) protein. The S protein is highly glycosylated and could be a target for lectins. Surfactant protein A (SP-A) is a collagen-containing C-type lectin, expressed by mucosal epithelial cells and mediates its antiv...

Powassan virus is a tickborne flavivirus that can cause lethal or debilitating neurologic illness. It is canonically transmitted by Ixodes spp. ticks but might spill over to sympatric Dermacentor species. We detected Powassan virus lineage I from a pool of field-collected D. variabilis ticks in New York, USA.

Ticks transmit several arthropod-borne pathogens in New York State. The primary human-biting ticks in this region are Ixodes scapularis , Amblyomma americanum , and Dermacentor variabilis . Body regions where tick bites human vary depending on the tick species and life stage, and clothing worn by the host. A community tick submission system was use...

Rift Valley fever (RVF) is a mosquito-borne zoonosis endemic to Africa and the Arabian Peninsula, which causes large outbreaks among humans and ruminants. Single dose vaccinations using live-attenuated RVF virus (RVFV) support effective prevention of viral spread in endemic countries. Due to the segmented nature of RVFV genomic RNA, segments of vac...

Ticks transmit several arthropod-borne pathogens in New York state. The primary human-biting ticks in this region are Ixodes scapularis , Amblyomma americanum , and Dermacentor variabilis . Tick body-segment preference varies depending on tick and host species, with the human bite-site located on the head or lower extremities and abdomen. A communi...

A community engaged passive surveillance program was utilized to acquire ticks and associated information throughout New York state. Ticks were speciated and screened for several tick-borne pathogens. Of these ticks, only I. scapularis was commonly infected with pathogens of human relevance, including B. burgdorferi, B. miyamotoi, A. phagocytophilu...

Arboviruses such as flaviviruses and alphaviruses cause a significant human healthcare burden on the global scale. Transmission of these viruses occurs during human blood feeding at the mosquito-skin interface. Not only do pathogen immune evasion strategies influence the initial infection and replication of pathogens delivered, but arthropod saliva...

Powassan virus (POWV) is a tick-borne flavivirus that can cause lethal or debilitating neurological illness. It is canonically transmitted by Ixodes genus ticks but may interact with sympatric Dermacentor species. Here, we report the first detection of POWV lineage I from a pool of field-collected D. variabilis in New York state.

Objectives: We sought to determine the habitat associations and pathogen status of Amblyomma maculatum ticks in New York City, New York, USA, a newly expanded portion of their range. Methods: We collected 88 ticks from two New York City parks on Staten Island, one of the five boroughs of New York City, and compared our findings to similar habitat...

Zoonotic viruses threaten the lives of millions of people annually, exacerbated by climate change, human encroachment into wildlife habitats, and habitat destruction. The Powassan virus (POWV) is a rare tick-borne virus that can cause severe neurological damage and death, and the incidence of the associated disease (Powassan virus disease) is incre...

Powassan virus (POWV) is a neuroinvasive flavivirus transmitted to mammals by the bite of ixodid ticks. In this study, we sought to investigate the impact of tick salivary gland extract (SGE) on POWV neuroinvasion. BALB/c mice were footpad inoculated with either a high dose or a low dose of POWV, with and without Ixodes scapularis salivary gland ex...

A chimeric Eilat/ Chikungunya virus (EILV/CHIKV) was previously reported to replicate only in mosquito cells but capable of inducing robust adaptive immunity in animals. Here, we initially selected C7/10 cells to optimize the production of the chimeric virus. A two-step procedure produced highly purified virus stocks, which was shown to not cause h...

Ticks are the primary vector of arboviruses in temperate climates worldwide. They are both the vector of these pathogens to humans and an integral component of the viral sylvatic cycle. Understanding the tick‐pathogen interaction provides information about the natural maintenance of these pathogens and informs the development of countermeasures aga...

The detection of novel or re-emergent pathogens necessitates the development of rapid, easy-to-use diagnostic tests that can be readily adapted and utilized in both clinical laboratories and field settings. Heartland virus (HRTV) is the first pathogenic Phlebovirus responsible for serious and fatal cases in the United States. We developed a qualita...

The name of the first author in the article by Tulisas et al.[(2009), Acta Cryst. F65, 533–535] is corrected.

Powassan virus (POWV) is a tick-borne flavivirus that encompasses two genetic lineages, POWV (Lineage I) and deer tick virus (DTV, Lineage II). In recent years, the incidence of reported POWV disease cases has increased, coupled with an expanded geographic range of the DTV tick vector, Ixodes scapularis. POWV and DTV are serologically indistinguish...

Mutations are incorporated into the genomes of RNA viruses at an optimal frequency and altering this precise frequency has been proposed as a strategy to create live-attenuated vaccines. However, determining the effect of specific mutations that alter fidelity has been difficult because of the rapid selection of the virus population during replicat...

Skin is the interface between an attached, feeding tick and a host; consequently, it is the first line of defense against invading pathogenic microorganisms that are delivered to a vertebrate host together with tick saliva. Central to the successful transmission of a tick-borne pathogen are complex interactions between the host immune response and...

Ticks are hematophagous arthropods that transmit a number of pathogens while feeding. Among these is tick-borne encephalitis virus (TBEV), a flavivirus transmitted by Ixodes ricinus ticks in the temperate zone of Europe. The infection results in febrile illness progressing to encephalitis and meningitis with a possibility of fatality or long-term n...

Cases of tick-borne diseases, including spotted fever rickettsioses, borreliosis, babesiosis, anaplasmosis and ehrlichiosis, in the United States and territories have more than doubled from 2004 to 2016 and account for 77% of all vector-borne disease reports. In an effort to inform control efforts, the presence of tick-borne pathogens and their vec...

Successful tick feeding is facilitated by an assortment of pharmacologically-active factors in tick saliva that create an immunologically privileged micro-environment in the host’s skin. Through a process known as saliva-assisted transmission, bioactive tick salivary factors modulate the host environment, promoting transmission and establishment of...

The presence of bottlenecks in the transmission cycle of many RNA viruses leads to a severe reduction of number of virus particles and this occurs multiple times throughout the viral transmission cycle. Viral replication is then necessary for regeneration of a diverse mutant swarm. It is now understood that any perturbation of the mutation frequenc...

The changes in growth curves at an MOI of 0.01 and 10 for passage 1 and passage 5 viruses and the sensitivity to 5FU following passage 5 compared to passage 1. (TIFF)

Showing the numbers and graph of the mosquitoes assessed for dissemination on individual days. (TIFF)

The relationship of titer to clone for A, B & C infections with low dose for G7R, 3x and 4x RdRp mutants, respectively. D, E & F, infections with high dose for G7R, 3x and 4x RdRp mutants, respectively. All titers were calculated from using standard curves run concurrently with the samples. G. The correlation between number of clones and titer for...

Comparison of the fidelity mutants to the wild type for bodies. A). At 10^6 pfu/ml infection where the bodies were statistically different from the wild-type by two way ANOVA at P<0.0001, all fidelity clones showed differences from the wild-type by Dunnetts multiple comparisons test. B). At 10^5 pfu/ml infection where the bodies were statistically...

The number of stop codons produced along the genome. The genome was sub-divided into 100 bins and the first column corresponds to the bin centers for that bin. This table was used to produce Fig 2C. (DOCX)

The changes in mutation frequency for each individual cell type. The table shows the significance as determined by two-way ANOVA p<0.0001. Individual changes are found in the table. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. (TIFF)

The number of 68U201 marked clones present in the tissues of mice on days 1–7 post infection. Mice were infected with an equal mixture of 8 clones and perfused to remove infected blood before tissues were sampled. (TIFF)

1. Introduction 2. The need for tick genome resources 3. Data-driven solutions for tick and tick-borne disease control 3.1. The systems biology of tick-host-pathogen interactions 3.2. The link between tick genetics, vector competence and disease transmission 3.3. Genetic frameworks for Ixodes control 4. The Ix1000G roadmap 4.1. Priority area 1: Hig...

Tick-borne viral diseases continue to emerge in the United States, as clearly evident from the increase in Powassan encephalitis virus, Heartland virus, and Bourbon virus infections. Tick-borne flaviviruses (TBFVs) are transmitted to the mammalian host along with the infected tick saliva during blood-feeding. Successful tick feeding is facilitated...

The Flavivirus genus comprises a diverse group of viruses that utilize a wide range of vertebrate hosts and arthropod vectors. The genus includes viruses that are transmitted solely by mosquitoes or vertebrate hosts as well as viruses that alternate transmission between mosquitoes or ticks and vertebrates. Nevertheless, the viral genetic determinan...

Chlamydomonas reinhardtii (Chlamydomonas) strains that are toxic to mosquito larvae because they express chloroplast transgenes that are based on the mosquitocidal proteins of Bacillus thuringiensis subsp. israelensis (Bti) could be very useful in mosquito control. Chlamydomonas has several advantages for this approach, including genetic controls n...

Emerging and re-emerging diseases transmitted by blood feeding arthropods are significant global public health problems. Ticks transmit the greatest variety of pathogenic microorganisms of any blood feeding arthropod. Infectious agents transmitted by ticks are delivered to the vertebrate host together with saliva at the bite site. Tick salivary gla...

Heartland virus (HRTV) is an emerging tick-borne virus (Bunyaviridae, Phlebovirus) that has caused sporadic cases of human disease in several central and mid-eastern states of America. Animal models of HRTV disease are needed to gain insights into viral pathogenesis and advancing antiviral drug development. Presence of clinical disease following HR...

Ticks are efficient vectors of arboviruses, although less than 10% of tick species are known to be virus vectors. Most tick-borne viruses (TBV) are RNA viruses some of which cause serious diseases in humans and animals world-wide. Several TBV impacting human or domesticated animal health have been found to emerge or re-emerge recently. In order to...

Zika virus (ZIKV), a flavivirus transmitted primarily by Aedes aegypti, has recently spread globally in an unprecedented fashion, yet we have a poor understanding of host-microbe interactions in this system. To gain insights into the interplay between ZIKV and the mosquito, we sequenced the small RNA profiles in ZIKV-infected and non-infected Ae. a...

Zika virus (ZIKV), a flavivirus transmitted primarily by Aedes aegypti, has recently spread globally in an unprecedented fashion, yet we have a poor understanding of host-microbe interactions in this system. To gain insights into the interplay between ZIKV and the mosquito, we sequenced the small RNA profiles in ZIKV-infected and non-infected Ae. a...

Small RNA read summary in ZIKV-infected and non-infected libraries. (DOCX)

Viral quantification of individual mosquitoes used for high throughput sequencing. (PDF)

Average Ct values of the U6B small nuclear RNA in Zika virus infected and uninfected mosquitoes at days 2, 7, and 14 post infection. (PDF)

Predicted transcripts modulated by miRNAs. (XLSX)

Potential interactions between the host differentially expressed miRNAs and the ZIKV genome. (DOCX)

Primer sequences for qPCR. (DOCX)

We are developing Chlamydomonas strains that can be used for safe and sustainable control of mosquitoes, because they produce proteins from Bacillus thuringiensis subsp. israelensis (Bti) in the chloroplast. Chlamydomonas has a number of advantages for this approach, including genetic controls that are not generally available with industrial algae....

Arthropod-borne viruses (arboviruses) have continued to emerge in recent years, posing a significant health threat to millions of people worldwide. The majority of arboviruses that are pathogenic to humans are transmitted by mosquitoes and ticks, but other types of arthropod vectors can also be involved in the transmission of these viruses. To alle...

Powassan virus (POWV, Flaviviridae) is the only North American member of the tick-borne encephalitis serogroup of flaviviruses. It is transmitted to small- and medium-sized mammals by Ixodes scapularis, Ixodes cookei, and several other Ixodes tick species. Humans become infected with POWV during spillover transmission from the natural transmission...

During the past two decades, there has been a dramatic increase in the recognition and characterization of novel insect-specific flaviviruses (ISFVs). Some of these agents are closely related to important mosquito-borne flavivirus pathogens. Results of experimental studies suggest that mosquitoes and mosquito cell cultures infected with some ISFVs...

Zika virus has recently spread throughout the Americas. Although Aedes aegypti mosquitoes are considered the primary vector, Culex quinquefasciatus and mosquitoes of other species may also be vectors. We tested Cx. quinquefasciatus and Ae. taeniorhynchus mosquitoes from the US Gulf Coast; both were refractory to infection and incapable of transmiss...

Tick-borne viruses include medically important zoonotic pathogens that can cause life-threatening diseases. Unlike mosquito-borne viruses, whose impact can be restrained via mosquito population control programs, for tick-borne viruses only vaccination remains the reliable means of disease prevention. For live vaccine viruses a concern exists, that...

Previous experimental studies have demonstrated that a number of mosquito-borne flavivirus pathogens are vertically transmitted in their insect vectors, providing a mechanism for these arboviruses to persist during adverse climatic conditions or in the absence of a susceptible vertebrate host. In this study, designed to test whether Zika virus (ZIK...

Powassan virus (POWV) belongs to the family Flaviviridae and is a member of the tick-borne encephalitis serogroup. Transmission of POWV from infected ticks to humans has been documented in the USA, Canada, and Russia, causing fatal encephalitis in 10% of human cases and significant neurological sequelae in survivors. We used C57BL/6 mice to investi...

Powassan virus (POWV) is a tick-borne flavivirus that can result in a severe neuroinvasive disease with 50% of survivors displaying long-term neurological sequelae. Human POWV cases have been documented in Canada, the United States, and Russia. Although the number of reported POWV human cases has increased in the past fifteen years, POWV remains on...

Powassan virus (POWV) is an encephalitic tick-borne flavivirus which can result in serious neuroinvasive disease with up to a 10% case fatality rate. The study objective was to determine whether the salivary gland extract (SGE) from Ixodes scapularis ticks facilitates the transmission and dissemination of POWV in a process known as saliva-activated...

Author Summary Mosquito saliva contains a complex repertoire of bioactive factors that are secreted into blood feeding site, the skin. Infected mosquitoes transmit pathogens to the host during feeding via saliva. The bioactive factors in mosquito saliva are responsible for modulating host hemostasis, immune defenses and pain/itch responses, and hav...

Recently, there has been a dramatic increase in the detection and characterization of insect-specific viruses in field-collected mosquitoes. Evidence suggests that these viruses are ubiquitous in nature and that many are maintained by vertical transmission in mosquito populations. Some studies suggest that the presence of insect-specific viruses ma...

Emerging Microbes and Infections (EMI) is a new open access, fully peer-reviewed journal that will publish the best and most interesting research in emerging microbes and infectious disease.

Tick borne diseases continue to emerge and have a great impact on public health and agriculture. In addition, many of the tick borne diseases agents, which are classified as Biosafety Level 4 (BSL-4) viruses, have the potential to be used as biothreat agents. In spite of the known importance of these pathogens, there is an acute shortage of facilit...

Tick salivary glands produce complex cocktails of bioactive molecules that facilitate blood feeding and pathogen transmission by modulating host hemostasis, pain/itch responses, wound healing, and both innate and adaptive immunity. In this study, cutaneous responses at Dermacentor andersoni bite-sites were analyzed using Affymetrix mouse genome arr...

##Assembly-Data-START## Assembly Method :: Bowtie v. 1 Sequencing Technology :: Illumina ##Assembly-Data-END##

Abbreviations: POWV, Powassan virus; TNF, tumor necrosis factor

Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the most geographically widespread arboviruses and causes a severe hemorrhagic syndrome in humans. The virus circulates in nature in a vertebrate-tick cycle and ticks of the genus Hyalomma are the main vectors and reservoirs. Although the tick vector plays a central role in the maintenance and...

Ixodes species ticks are competent vectors of tick-borne viruses including tick-borne encephalitis and Powassan encephalitis. Tick saliva has been shown to facilitate and enhance viral infection. This likely occurs by saliva-mediated modulation of host responses into patterns favorable for viral infection and dissemination. Because of the rapid kin...

Histopathology of Ixodes scapularis nymphal bite sites at 1 hr PI. Skin biopsies were fixed in formaldehyde prior to decalcification and paraffin embedding. Sections were stained with Geimsa, as described in methods section. Mast cells appear as collections of dark purple granules. (TIF)

Correlation between the microarray and the real-time PCR analysis. FC, fold change; P val, p-value; hpi, hours post-infestation. (DOCX)

Ixodes scapularis ticks are hematophagous arthropods capable of transmitting many infectious agents to humans. The process of blood feeding is an extended and continuous interplay between tick and host responses. While this process has been studied extensively in vitro, no global understanding of the host response to ticks has emerged. To address t...

Gene groups used to allow comparisons between time points. All 233 genes measured in this study were grouped based on characteristics of the encoded protein. These groups were used to allow comparisons between time points throughout our study.

Direct comparison of PCR array and qRT-PCR validation experiments. Fold change and p-values obtained from the PCR array and qRT-PCR validation experiments are directly compared. "Primary" refers to primary infestation, while "secondary" refers to the secondary exposure. A "+" marks fold changes calculated from transcripts below the detection limit...

Statistical comparison between primary and secondary infestations. Significant changes in gene expression between primary and secondary infestation were measured using LIMMA and the same filtering criteria as before (Methods). Each column shows the genes significantly modulated over the primary infestation during a secondary exposure of mice to I....

Comparison of PCR array, qRT-PCR validation, and protein expression levels. Gene expression and protein levels were compared by transforming protein expression data into fold change in fluorescence intensity over control samples. "ns" refers to non-significant results (p-value > 0.01 for gene expression and > 0.05 for protein expression); "+" denot...

List of genes measured by qRT-PCR for validation of PCR array results.

Outbreaks of Mayaro fever have been associated with a sylvatic cycle of Mayaro virus (MAYV) transmission in South America. To evaluate the potential for a common urban mosquito to transmit MAYV, laboratory vector competence studies were performed with Aedes aegypti from Iquitos, Peru. Oral infection in Ae. aegypti ranged from 0% (0/31) to 84% (31/3...

Surface representation for Furin and Subtilisin, and backbone trace representation for CrSPI-1 of the heterotrimer model. (TIF)

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