About

Shengzhang Dong, PhD, MS, is an Assistant Scientist at Johns Hopkins Bloomberg School of Public Health, affiliated with the Department of Molecular Microbiology and Immunology and the Johns Hopkins Malaria Research Institute. His research focuses on developing novel control strategies for mosquito-borne diseases such as dengue and malaria through the study of mosquito biology, genomics, and pathogen interactions. Dr. Dong's work involves mosquito genome editing, transgenic mosquitoes, and understanding mosquito-pathogen interactions to create sustainable vector control methods. He holds a PhD from Zhejiang University obtained in 2007, an MS from Anhui Agricultural University in 2004, and a BS from the same university in 2001. His research aims to address the global health challenge posed by mosquito-borne diseases, which cause over one million deaths annually. Dr. Dong's contributions include engineering broad-spectrum suppression of arboviruses in mosquitoes and exploring the molecular mechanisms of mosquito immunity and reproduction, with the ultimate goal of reducing disease transmission.

Research topics

• Biology
• Genetics
• Immunology
• Virology
• Microbiology

Selected publications

• Engineered antibody-mediated broad-spectrum suppression of human arboviruses in the Aedes aegypti vector

  Communications Biology · 2025-05-07 · 4 citations

  articleOpen access1st authorCorresponding

  Mosquito-borne orthoflaviviruses such as dengue and Zika viruses, and alphaviruses such as chikungunya viruses continue to pose global health threats, necessitating innovative vector control strategies. Small antibodies (sAb) such as single-chain variable fragments (scFv) and single-domain antibodies (sdAb) against dengue and chikungunya viral proteins have been applied to neutralize viral infections in mouse and human primary cells. Here, we explored the use of these protective sAbs for the development of transgenic mosquito-based arboviral disease control strategies. We expressed scFv against orthoflaviviruses and sdAb against alphaviruses using a dual bloodmeal-inducible midgut-specific promoter, AeG12, achieving strong expression of both orthoflavivirus scFv and alphavirus sdAb in Aedes aegypti midguts. The presence of sAbs significantly reduced mosquito midgut infections with multiple orthoflaviviruses and alphaviruses, such as dengue, Zika, chikungunya and Mayaro viruses, thus compromising viral transmission by the transgenic mosquitoes. We further augmented virus-blocking by co-expression of sAbs and the siRNA pathway factor Dcr2, proving the utility of combinatorial virus targeting by mechanistically independent antiviral effectors. Our results demonstrate the potential of expressing broadly neutralizing sAbs in mosquitoes, particularly in combination with enhancing endogenous antiviral pathways, as a promising strategy to reduce arbovirus transmission by mosquitoes.

  PublisherOA PDFDOI

• Enhancing Tissue-Specific Antiviral Immunity to Disrupt Arbovirus Transmission by Mosquitoes

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-04

  preprintOpen access1st author

  Abstract Arboviruses, including dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV), pose a significant global health and economic burden, with Aedes aegypti serving as their primary vector. Arbovirus infection in Ae. aegypti progresses sequentially through the midgut (MG), carcass (CA), and salivary glands (SG), with each tissue exhibiting distinct antiviral responses. Here, we investigate tissue-specific antiviral mechanisms, focusing on the small interfering RNA (siRNA) pathway in SGs. Our results reveal that SGs possess weaker antiviral defense and are more susceptible to arboviral infection compared to MGs and CAs. Notably, overexpression of Dicer2 ( Dcr2 ), a key component of the siRNA pathway, in SGs leads to a significant decrease in arboviral replication. Conversely, Dcr2 overexpression in fat bodies, the primary tissue in CAs, only moderately suppresses DENV2 infection and has no notable effect on Mayaro virus (MAYV) infection. Remarkably, the simultaneous overexpression of Dcr2 in both MGs and SGs enhances antiviral activity, effectively blocking the transmission of multiple arboviruses. These findings reveal the tissue-specific dynamics of mosquito antiviral immunity and underscore the potential for targeting SG-specific immunity to disrupt arbovirus transmission, providing a promising approach for controlling mosquito-borne diseases.

  PublisherOA PDFDOI

• Isolation, identification and genetic variation analysis of pseudorabies virus mutant strain from Chinese pig farm

  Journal of the Hellenic Veterinary Medical Society · 2024-07-10

  articleOpen access

  ABSTRACT: Pseudorabies (PR) is an important infectious disease affecting pig farms worldwide. In this study, we reported a pseudorabies virus (PRV) isolated from a Bartha-K61-vaccinated pig farm in Linyi, Shandong Province, China. Evidence from virus isolation, electronic microscope observation，laboratory animal infection, and histopathologic examination confirmed that the etiological agent of the disease is PRV SD-2017. Sequence alignment of the gE gene indicated that it belongs to a new mutated PRV strain. The gB sequence alignment showed that compared with the Bartha and Kaplan genotype 1 strains, SD-2017 strain had a deletion of three amino acids at positions 75-78 (SPG) and an insertion of one amino acid at position 94 (G). The gC gene had 7 amino acids (A, A, A, S, T, P and A) inserted at positions 69-75 in comparison with the Bartha-K61 vaccine strain. The median lethal dose (LD50) of PRV SD-2017 strain on rabbits was 3.16×102.0TCID50/ml by Karber method. Histopathologic examinations showed that multiple lesion sites were observed in brains, lungs, livers and kidneys. PRV SD-2017 is different from other reports and should be paid more attention to avoid economic losses. Keywords: Pseudorabies virus; Sequence alignment; Amino acid mutations；Mutant strain

  PublisherDOI

• Wolbachia infection-responsive immune genes suppress Plasmodium falciparum infection in Anopheles stephensi

  PLoS Pathogens · 2024-04-10 · 18 citations

  articleOpen accessCorresponding

  Wolbachia, a maternally transmitted symbiotic bacterium of insects, can suppress a variety of human pathogens in mosquitoes, including malaria-causing Plasmodium in the Anopheles vector. However, the mechanistic basis of Wolbachia-mediated Plasmodium suppression in mosquitoes is not well understood. In this study, we compared the midgut and carcass transcriptomes of stably infected Anopheles stephensi with Wolbachia wAlbB to uninfected mosquitoes in order to discover Wolbachia infection-responsive immune genes that may play a role in Wolbachia-mediated anti-Plasmodium activity. We show that wAlbB infection upregulates 10 putative immune genes and downregulates 14 in midguts, while it upregulates 31 putative immune genes and downregulates 15 in carcasses at 24 h after blood-fed feeding, the time at which the Plasmodium ookinetes are traversing the midgut tissue. Only a few of these regulated immune genes were also significantly differentially expressed between Wolbachia-infected and non-infected midguts and carcasses of sugar-fed mosquitoes. Silencing of the Wolbachia infection-responsive immune genes TEP 4, TEP 15, lysozyme C2, CLIPB2, CLIPB4, PGRP-LD and two novel genes (a peritrophin-44-like gene and a macro domain-encoding gene) resulted in a significantly greater permissiveness to P. falciparum infection. These results indicate that Wolbachia infection modulates mosquito immunity and other processes that are likely to decrease Anopheles permissiveness to Plasmodium infection.

  PublisherOA PDFDOI

• Long non-coding RNAs regulate Aedes aegypti vector competence for Zika virus and reproduction

  PLoS Pathogens · 2023-06-15 · 12 citations

  articleOpen accessCorresponding

  Long non-coding RNAs (lncRNAs) play critical regulatory roles in various cellular and metabolic processes in mosquitoes and all other organisms studied thus far. In particular, their involvement in essential processes such as reproduction makes them potential targets for the development of novel pest control approaches. However, their function in mosquito biology remains largely unexplored. To elucidate the role of lncRNAs in mosquitoes' reproduction and vector competence for arboviruses, we have implemented a computational and experimental pipeline to mine, screen, and characterize lncRNAs related to these two biological processes. Through analysis of publicly available Zika virus (ZIKV) infection-regulated Aedes aegypti transcriptomes, at least six lncRNAs were identified as being significantly upregulated in response to infection in various mosquito tissues. The roles of these ZIKV-regulated lncRNAs (designated Zinc1, Zinc2, Zinc3, Zinc9, Zinc10 and Zinc22), were further investigated by dsRNA-mediated silencing studies. Our results show that silencing of Zinc1, Zinc2, and Zinc22 renders mosquitoes significantly less permissive to ZIKV infection, while silencing of Zinc22 also reduces fecundity, indicating a potential role for Zinc22 in trade-offs between vector competence and reproduction. We also found that silencing of Zinc9 significantly increases fecundity but has no effect on ZIKV infection, suggesting that Zinc9 may be a negative regulator of oviposition. Our work demonstrates that some lncRNAs play host factor roles by facilitating viral infection in mosquitoes. We also show that lncRNAs can influence both mosquito reproduction and permissiveness to virus infection, two biological systems with important roles in mosquito vectorial capacity.

  PublisherOA PDFDOI

• Aedes aegypti Argonaute 2 controls arbovirus infection and host mortality

  Nature Communications · 2023-09-18 · 42 citations

  articleOpen access1st authorCorresponding

  Ae. aegypti mosquitoes transmit some of the most important human viral diseases that are responsible for a significant public health burden worldwide. The small interfering RNA (siRNA) pathway is considered the major antiviral defense system in insects. Here we show that siRNA pathway disruption by CRISPR/Cas9-based Ago2 knockout impaired the mosquitoes' ability to degrade arbovirus RNA leading to hyper-infection accompanied by cell lysis and tissue damage. Ago2 disruption impaired DNA repair mechanisms and the autophagy pathway by altering histone abundance. This compromised DNA repair and removal of damaged cellular organelles and dysfunctional aggregates promoted mosquito death. We also report that hyper-infection of Ago2 knockout mosquitoes stimulated a broad-spectrum antiviral immunity, including apoptosis, which may counteract infection. Taken together, our studies reveal novel roles for Ago2 in protecting mosquitoes from arbovirus infection and associated death.

  PublisherOA PDFDOI

• Trypsin-like Inhibitor Domain (TIL)-Harboring Protein Is Essential for Aedes aegypti Reproduction

  International Journal of Molecular Sciences · 2022-07-13 · 9 citations

  articleOpen access

  Cysteine-rich trypsin inhibitor-like domain (TIL)-harboring proteins are broadly distributed in nature but remain understudied in vector mosquitoes. Here we have explored the biology of a TIL domain-containing protein of the arbovirus vector Aedes aegypti, cysteine-rich venom protein 379 (CRVP379). CRVP379 was previously shown to be essential for dengue virus infection in Ae. aegypti mosquitoes. Gene expression analysis showed CRVP379 to be highly expressed in pupal stages, male testes, and female ovaries. CRVP379 expression is also increased in the ovaries at 48 h post-blood feeding. We used CRISPR-Cas9 genome editing to generate two mutant lines of CRVP379 with mutations inside or outside the TIL domain. Female mosquitoes from both mutant lines showed severe defects in their reproductive capability; mutant females also showed differences in their follicular cell morphology. However, the CRVP379 line with a mutation outside the TIL domain did not affect male reproductive performance, suggesting that some CRVP379 residues may have sexually dimorphic functions. In contrast to previous reports, we did not observe a noticeable difference in dengue virus infection between the wild-type and any of the mutant lines. The importance of CRVP379 in Ae. aegypti reproductive biology makes it an interesting candidate for the development of Ae. aegypti population control methods.

  PublisherOA PDFDOI

• The Role of Mosquito Hemocytes in Viral Infections

  Viruses · 2022-09-20 · 29 citations

  reviewOpen access

  Insect hemocytes are the only immune cells that can mount a humoral and cellular immune response. Despite the critical involvement of hemocytes in immune responses against bacteria, fungi, and parasites in mosquitoes, our understanding of their antiviral potential is still limited. It has been shown that hemocytes express humoral factors such as TEP1, PPO, and certain antimicrobial peptides that are known to restrict viral infections. Insect hemocytes also harbor the major immune pathways, such as JAK/STAT, TOLL, IMD, and RNAi, which are critical for the control of viral infection. Recent research has indicated a role for hemocytes in the regulation of viral infection through RNA interference and autophagy; however, the specific mechanism by which this regulation occurs remains uncharacterized. Conversely, some studies have suggested that hemocytes act as agonists of arboviral infection because they lack basal lamina and circulate throughout the whole mosquito, likely facilitating viral dissemination to other tissues such as salivary glands. In addition, hemocytes produce arbovirus agonist factors such as lectins, which enhance viral infection. Here, we summarize our current understanding of hemocytes' involvement in viral infections.

  PublisherOA PDFDOI

• The Aedes aegypti siRNA pathway mediates broad-spectrum defense against human pathogenic viruses and modulates antibacterial and antifungal defenses

  PLoS Biology · 2022 · 37 citations

  • Biology
  • Virology
  • Microbiology

  The mosquito's innate immune system defends against a variety of pathogens, and the conserved siRNA pathway plays a central role in the control of viral infections. Here, we show that transgenic overexpression of Dicer2 (Dcr2) or R2d2 resulted in an accumulation of 21-nucleotide viral sequences that was accompanied by a significant suppression of dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) replication, thus indicating the broad-spectrum antiviral response mediated by the siRNA pathway that can be applied for the development of novel arbovirus control strategies. Interestingly, overexpression of Dcr2 or R2d2 regulated the mRNA abundance of a variety of antimicrobial immune genes, pointing to additional functions of DCR2 and R2D2 as well as cross-talk between the siRNA pathway and other immune pathways. Accordingly, transgenic overexpression of Dcr2 or R2d2 resulted in a lesser proliferation of the midgut microbiota and increased resistance to bacterial and fungal infections.

  PublisherOA PDFDOI

• Antiviral Compounds for Blocking Arboviral Transmission in Mosquitoes

  Viruses · 2021-01-14 · 26 citations

  reviewOpen access1st author

  Mosquito-borne arthropod-borne viruses (arboviruses) such as the dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) are important human pathogens that are responsible for significant global morbidity and mortality. The recent emergence and re-emergence of mosquito-borne viral diseases (MBVDs) highlight the urgent need for safe and effective vaccines, therapeutics, and vector-control approaches to prevent MBVD outbreaks. In nature, arboviruses circulate between vertebrate hosts and arthropod vectors; therefore, disrupting the virus lifecycle in mosquitoes is a major approach for combating MBVDs. Several strategies were proposed to render mosquitoes that are refractory to arboviral infection, for example, those involving the generation of genetically modified mosquitoes or infection with the symbiotic bacterium Wolbachia. Due to the recent development of high-throughput screening methods, an increasing number of drugs with inhibitory effects on mosquito-borne arboviruses in mammalian cells were identified. These antivirals are useful resources that can impede the circulation of arboviruses between arthropods and humans by either rendering viruses more vulnerable in humans or suppressing viral infection by reducing the expression of host factors in mosquitoes. In this review, we summarize recent advances in small-molecule antiarboviral drugs in mammalian and mosquito cells, and discuss how to use these antivirals to block the transmission of MBVDs.

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Frequent coauthors

• Cui Hu

  Northeast Institute of Geography and Agroecology

  47 shared

• Zhicheng Shen

  Hangzhou DAC Biotech (China)

  18 shared

• Gong‐Yin Ye

  Zhejiang University

  18 shared

• Alexander W. E. Franz

  University of Missouri

  16 shared

• Gong-Yin Ye

  Zhejiang University

  16 shared

• Gōngyín Yè

  16 shared

• Xiaoping Yu

  Chengdu University

  15 shared

• George Dimopoulos

  Johns Hopkins University

  13 shared

Education

• Ph.D, Entomology

  Zhejiang University

  2007

• Master, Biology

  Anhui Agricultural University

  2004

• Bachelor, Biology

  Anhui Agricultural University

  2001