Vector biology meets disease control: using basic research to fight vector-borne diseases

Shaw, W. Robert; Catteruccia, Flaminia

doi:10.1038/s41564-018-0214-7

Cited by 211 publications

(211 citation statements)

References 192 publications

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“…Targeting the vector. Progress has been made in reducing flavivirus transmission by limiting infection of the mosquito host 281 . For example, the infection of A. aegypti mosquitoes with selected strains of endosymbiotic Wolbachia resulted in bacterial invasion of mosquito populations and interference with DENV and ZIKV replication 282,283 .…”

Section: Flavivirus Vaccinesmentioning

confidence: 99%

The continued threat of emerging flaviviruses

Pierson

Diamond²

2020

Nat Microbiol

658

627

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F laviviruses are single-stranded RNA viruses vectored principally by arthropods that cause severe illnesses in humans. The extensive global spread and epidemic transmission of flaviviruses during the last seven decades has been remarkable. The mosquito-borne dengue viruses (DENV) infect an estimated 400 million humans each year; more than a quarter of the world's population lives in areas where DENV is now endemic 1 . By comparison, only sporadic DENV epidemics were documented before the Second World War 2 . The introductions of West Nile (WNV) and Zika (ZIKV) viruses into the Western Hemisphere was followed by rapid geographical spread, large numbers of human infections and considerable morbidity 3,4 . Ongoing yellow fever virus (YFV) transmission and its encroachment on urban environments, despite the existence of an effective vaccine, poses a serious public health challenge 5-7 . Other flaviviruses present ongoing health risks or are beginning to emerge in different parts of the world, including Japanese encephalitis virus (JEV), tick-borne encephalitis virus (TBEV) and Usutu virus (USUV).The epidemic potential of flaviviruses reflects many factors related to the unique characteristics of their insect vectors, the consequences of poorly planned urbanization that creates ideal arthropod breeding habitats, the geographical expansion of vectors, changing environmental conditions and extensive global travel 8,9 . Beyond arthropods and humans, flaviviruses are also known to infect a wide array of animal species and can be important veterinary pathogens that threaten economically important domesticated animals 10-14 . These vertebrate animal hosts may constitute important stable reservoirs and contribute to defining conditions that support the introduction of new viral species and transmission among humans 15 . The continued threat of flavivirus emergence and re-emergence highlights a need for a detailed fundamental understanding of the biology of these viruses, the immune responses that can contain them and the possible countermeasures that can blunt their impact on public health should new outbreaks occur. Flavivirus structure and replicationFlaviviruses are small (~50 nm) spherical virus particles that incorporate a single genomic RNA of positive-sense polarity encoding three structural and seven non-structural proteins (Fig. 1a). Our knowledge of the biology of flaviviruses has advanced considerably with the availability of high-resolution structures of viral structural proteins and of virions at different stages of the replication cycle or in complex with antibodies or host factors 16 . Crystal structures of the enzymatic non-structural proteins also have been solved, accelerating advances in an understanding of virus replication and pathogenesis [17][18][19] and enabling structure-guided drug discovery, as reviewed elsewhere 20 .Virion structure and morphogenesis. Flaviviruses are assembled using three viral structural proteins (C, prM and E), a host lipid envelope and the viral genomic RNA. The structure of ...

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Section: Flavivirus Vaccinesmentioning

confidence: 99%

The continued threat of emerging flaviviruses

Pierson

Diamond²

2020

Nat Microbiol

658

627

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“…Plasmodium parasites are transmitted between hosts by an infected female Anopheles mosquito (reviewed in 3 ). Following uptake of male and female gametocytes by the mosquito during a blood meal of an infected host, these parasites activate into male and female gametes in the midgut, fuse into a zygote, and develop into a motile ookinete, which burrows through the midgut wall and establishes an oocyst under the basal lamina.…”

Section: Introductionmentioning

confidence: 99%

Extensive Transcriptional and Translational Regulation Occur During the Maturation of Malaria Parasite Sporozoites

Lindner

Swearingen

Shears

et al. 2019

Preprint

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22 Introduction: 41Malaria remains one of the great global health problems today, taking a large toll on people in the 42 tropics and subtropics. This disease, caused by Plasmodium parasites, affects over 200 million people 43 annually and kills over 400,000 (WHO World Malaria Report 2018). While a protein-based subunit 44 vaccine (RTS,S) has recently been licensed and is being used for pilot implementation in three Saharan African countries, its protection has been limited and relatively short-lived in clinical trials 1 . 46 Identifying and fully testing an effective and long-lasting malaria vaccine remains a chief goal that has 47 yet to be achieved. Accomplishing this will require greater knowledge of the basic biology of the pre-48 erythrocytic sporozoite and liver stage parasites. Promising new whole-parasite vaccine candidates, 49 based upon the sporozoite form of the parasite, are on the horizon and hopefully will meet these needs 50 2 . 51Plasmodium parasites are transmitted between hosts by an infected female Anopheles mosquito 52 (reviewed in 3 ). Following uptake of male and female gametocytes by the mosquito during a blood meal 53 of an infected host, these parasites activate into male and female gametes in the midgut, fuse into a 54 zygote, and develop into a motile ookinete, which burrows through the midgut wall and establishes an 55 oocyst under the basal lamina. Within the oocyst, the parasite undergoes sporogony to produce up to 56 five thousand oocyst sporozoites 4 . These oocyst sporozoites are weakly infectious if injected directly 57 into a naïve mammalian host 5 , but become highly infectious following proteolytic rupture of the oocyst 58 wall and transit through the mosquito hemocoel. Sporozoites further gain infectivity after invasion of 59 the salivary glands 5,6 . Interestingly, the gain of infectivity for the mammalian host is concomitant with a 60 loss of infectivity for the salivary glands. Within the glands, the sporozoites await transmission as 61 salivary gland sporozoites, which occurs when the mosquito takes its next blood meal. Infection of a 62 host begins with the injection of salivary gland sporozoites into the skin. Following this, sporozoites exit 63 the bite site in the skin, locate and enter the vasculature, and passively travel to the liver, where 64 sporozoites can productively infect hepatocytes, which initiates the life cycle progression in the 65 mammalian host 7 . Moreover, because relatively few sporozoites are injected during a mosquito bite 8 , 66 this transmission event bottleneck has been the focus of intervention efforts using drugs, subunit 67 vaccines, and attenuated whole parasite vaccines 2 . 68Fundamental studies of sporozoite biology have informed efforts to inhibit and/or arrest the parasite 69 during development. To date, genetically-attenuated parasite (GAP) vaccine candidates were generated 70 by the deletion of genes whose transcripts are Up-regulated in Infective (Salivary Gland) Sporozoites 71 (UIS). The UIS gene family was originally determi...

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“…albimanus infection with the 7G8 Brazilian strain was 68% and average oocyst production was 2 oocysts; such production was small compared to the FCB2 strain studied here (56 oocysts by day 12) and highlighted differences regarding compatibility between South American parasite strains and mosquitoes from the same region [11,68]. Mosquito innate immune defence mechanisms may influence midgut epithelial ookinete invasion [69,70]; mosquito immune responses could thus be related to the aforementioned study's findings. Gametocytaemia, mosquito midgut xanthurenic acid concentration, haemozoin concentration, temperature and other intrinsic mosquito characteristics also influenced FCB2 sporogony formation inside An.…”

Section: Discussionmentioning

confidence: 61%

Sexual forms obtained in a continuous in vitro cultured Colombian strain of Plasmodium falciparum (FCB2)

Ararat-Sarria

Prado

Camargo

et al. 2020

Malar J

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Background: The epidemiological control of malaria has been hampered by the appearance of parasite resistance to anti-malarial drugs and by the resistance of mosquito vectors to control measures. This has also been associated with weak transmission control, mostly due to poor control of asymptomatic patients associated with host-vector transmission. This highlights the importance of studying the parasite's sexual forms (gametocytes) which are involved in this phase of the parasite's life-cycle. Some African and Asian strains of Plasmodium falciparum have been fully characterized regarding sexual forms' production; however, few Latin-American strains have been so characterized. This study was aimed at characterizing the Colombian FCB2 strain as a gametocyte producer able to infect mosquitoes. Methods:Gametocyte production was induced in in vitro cultured P. falciparum FCB2 and 3D7 strains. Pfap2g and Pfs25 gene expression was detected in FCB2 strain gametocyte culture by RT-PCR. Comparative analysis of gametocytes obtained from both strains was made (counts and morphological changes). In vitro zygote formation from FCB2 gametocytes was induced by incubating a gametocyte culture sample at 27 °C for 20 min. A controlled Anopheles albimanus infection was made using an artificial feed system with cultured FCB2 gametocytes (14-15 days old). Mosquito midgut dissection was then carried out for analyzing oocysts. Results:The FCB2 strain expressed Pfap2g, Pfs16, Pfg27/25 and Pfs25 sexual differentiation-related genes after in vitro sexual differentiation induction, producing gametocytes that conserved the expected morphological features. The amount of FCB2 gametocytes produced was similar to that from the 3D7 strain. FCB2 gametocytes were differentiated into zygotes and ookinetes after an in vitro low-temperature stimulus and infected An. albimanus mosquitoes, developing to oocyst stage. Conclusions:Even with the history of long-term FCB2 strain in vitro culture maintenance, it has retained its sexual differentiation ability. The gametocytes produced here preserved these parasite forms' usual characteristics and An. albimanus infection capability, thus enabling its use as a tool for studying sexual form biology, An. albimanus infection comparative analysis and anti-malarial drug and vaccine development.

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Vector biology meets disease control: using basic research to fight vector-borne diseases

Cited by 211 publications

References 192 publications

The continued threat of emerging flaviviruses

The continued threat of emerging flaviviruses

Extensive Transcriptional and Translational Regulation Occur During the Maturation of Malaria Parasite Sporozoites

Sexual forms obtained in a continuous in vitro cultured Colombian strain of Plasmodium falciparum (FCB2)

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