The complement system has been thought to originate exclusively in the deuterostomes. Here, we show that the central complement components already existed in the primitive protostome lineage. A functional homolog of vertebrate complement 3, CrC3, has been isolated from a ‘living fossil’, the horseshoe crab ( Carcinoscorpius rotundicauda ). CrC3 resembles human C3 and shows closest homology to C3 sequences of lower deuterostomes. CrC3 and plasma lectins bind a wide range of microbes, forming the frontline innate immune defense system. Additionally, we identified CrC2/Bf, a homolog of vertebrate C2 and Bf that participates in C3 activation, and a C3 receptor‐like sequence. Furthermore, complement‐mediated phagocytosis of bacteria by the hemocytes of horseshoe crab was also observed. Thus, a primitive yet complex opsonic complement defense system is revealed in the horseshoe crab, a protostome species. Our findings demonstrate an ancient origin of the critical complement components and the opsonic defense mechanism in the Precambrian ancestor of bilateral animals.

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% (31/37), with blood meal virus titers between 3.4 log₁₀ and 7.3 log₁₀ plaque-forming units (PFU)/mL. Transmission of MAYV by 70% (21/30) of infected mosquitoes was shown by saliva collection and exposure to suckling mice. Amount of viral RNA in febrile humans, determined by real-time polymerase chain reaction, ranged from 2.7 to 5.3 log₁₀ PFU equivalents/mL. Oral susceptibility of Ae. aegypti to MAYV at titers encountered in viremic humans may limit opportunities to initiate an urban cycle; however, transmission of MAYV by Ae. aegypti shows the vector competence of this species and suggests potential for urban transmission.

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 cycles. In humans, POWV is the causative agent of a severe neuroinvasive illness with 50% of survivors displaying long-term neurological sequelae. POWV was recognized as a human pathogen in 1958 when a young boy died of severe encephalitis in Powassan, Ontario, and POWV was isolated from the brain autopsy of this case. Two distinct genetic lineages of POWV are now recognized: POWV (lineage I) and deer tick virus (lineage II). Since the index case in 1958, over 100 human cases of POWV have been reported, with an apparent rise in disease incidence in the past 16 years. This recent increase in cases may represent a true emergence of POWV in regions where the tick vector species are prevalent, or it could represent an increase in POWV surveillance and diagnosis. In the past 5 years, both basic and applied research for POWV disease has intensified, including phylogenetic studies, field surveillance, case studies, and animal model development. This review provides an overview of POWV, including the epidemiology, transmission, clinical disease, and diagnosis of POWV infection. Recent research developments and future priorities with regard to the disease are emphasized.

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 (ZIKV) could be vertically transmitted, female Aedes aegypti and Aedes albopictus were injected with ZIKV, and their F₁ adult progeny were tested for ZIKV infection. Six of 69 Ae. aegypti pools, comprised of a total of 1,738 F₁ adults, yielded ZIKV upon culture, giving a minimum filial infection rate of 1:290. In contrast, none of 803 F₁ Ae. albopictus adults (32 pools) yielded ZIKV. The MFIR for Ae. aegypti was comparable to MFIRs reported for other flaviviruses in mosquitoes, including dengue, Japanese encephalitis, yellow fever, West Nile, and St. Louis encephalitis viruses. The results suggest that vertical transmission may provide a potential mechanism for the virus to survive during adverse conditions.

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 survive in nature, TBV must infect and replicate in both vertebrate and tick cells, representing very different physiological environments. Information on molecular mechanisms that allow TBV to switch between infecting and replicating in tick and vertebrate cells is scarce. In general, ticks succeed in completing their blood meal thanks to a plethora of biologically active molecules in their saliva that counteract and modulate different arms of the host defence responses (haemostasis, inflammation, innate and acquired immunity, and wound healing). The transmission of TBV occurs primarily during tick feeding and is a complex process, known to be promoted by tick saliva constituents. However, the underlying molecular mechanisms of TBV transmission are poorly understood. Immunomodulatory properties of tick saliva helping overcome the first line of defence to injury and early interactions at the tick-host skin interface appear to be essential in successful TBV transmission and infection of susceptible vertebrate hosts. The local host skin site of tick attachment, modulated by tick saliva, is an important focus of virus replication. Immunomodulation of the tick attachment site also promotes co-feeding transmission of viruses from infected to non-infected ticks in the absence of host viraemia (non-viraemic transmission). Future research should be aimed at identification of the key tick salivary molecules promoting virus transmission, and a molecular description of tick-host-virus interactions and of tick-mediated skin immunomodulation. Such insights will enable the rationale design of anti-tick vaccines that protect against disease caused by tick-borne viruses.

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. aegypti mosquitoes at 2, 7 and 14 days post-infection. ZIKA induced an RNAi response in the mosquito with virus-derived short interfering RNAs and PIWI-interacting RNAs dramatically increased in abundance post-infection. Further, we found 17 host microRNAs (miRNAs) that were modulated by ZIKV infection at all time points. Strikingly, many of these regulated miRNAs have been reported to have their expression altered by dengue and West Nile viruses, while the response was divergent from that induced by the alphavirus Chikungunya virus in mosquitoes. This suggests that conserved miRNA responses occur within mosquitoes in response to flavivirus infection. This study expands our understanding of ZIKV-vector interactions and provides potential avenues to be further investigated to target ZIKV in the mosquito host. Vector-borne viruses have immense impacts on human health by causing mortality and morbidity. Control of diseases caused by these viruses have mostly concentrated on vector control or inhibition of virus transmission by the vectors. This requires a thorough understanding of vector-virus interactions. In this study, we investigated the RNA interference (RNAi) response in Aedes aegypti mosquitoes infected with the Zika virus (ZIKV) strain isolated from the current pandemic using deep sequencing technologies. We found that infection alters the microRNA (miRNA) profile between infected and uninfected mosquitoes and that changes in miRNA expression occur over time. The short interfering RNA pathway, which is the main mosquito defense as part of the RNAi pathway, was also induced by ZIKV infection with the number of short interfering RNAs increasing significantly as infection progressed. Our results indicate that ZIKV induces the mosquito host defense similar to infection with other flaviviruses.