Low density lipopolyprotein inhibits flavivirus acquisition in Aedes aegypti

Z L Wagar1, M O Tree1, M C Mpoy1

  • 1Foundational Sciences, Central Michigan University, College of Medicine, Mount Pleasant, MI, USA.

Insights

Low-density lipoprotein (LDL) inhibits dengue and Zika virus acquisition in Aedes aegypti mosquitoes. This finding suggests

Area of Science:

  • * Vector-borne disease research
  • * Medical entomology
  • * Virology

Background:

  • * Aedes aegypti mosquitoes transmit critical human pathogens like dengue virus (DENV) and Zika virus (ZIKV).
  • * Mosquitoes acquire these viruses from infected vertebrate bloodmeals, which contain factors influencing viral transmission.
  • * Reduced low-density lipoprotein (LDL) levels correlate with severe DENV infections, suggesting a potential role for LDL in flavivirus acquisition.

Purpose of the Study:

  • * To investigate the hypothesis that LDL is a modifiable factor influencing flavivirus acquisition in Aedes aegypti.
  • * To determine the cellular mechanisms of LDL uptake in mosquito cells and midgut epithelium.
  • * To evaluate the inhibitory effect of LDL on DENV and ZIKV infection in vitro and in vivo.

Main Methods:

  • * Investigated LDL endocytosis in Ae. aegypti cells using dynamin-dependent assays.
  • * Examined LDL accumulation in mosquito midgut epithelial cells during bloodmeal digestion.
  • * Assessed the impact of LDL and high-density lipoprotein (HDL) pretreatment on DENV and ZIKV infection rates in vitro and in vivo.

Main Results:

  • * LDL is endocytosed by Ae. aegypti cells in a dynamin-dependent manner.
  • * LDL accumulates in the midgut epithelium during bloodmeal digestion.
  • * LDL significantly inhibited DENV and ZIKV infection in vitro, and ZIKV infection in vivo, while HDL had no significant effect.

Conclusions:

  • * Human LDL, commonly known as 'bad cholesterol,' acts as an inhibitor of flavivirus acquisition in Aedes aegypti.
  • * This discovery highlights LDL as a modifiable factor with potential to disrupt vector-borne disease transmission.
  • * Understanding these cellular interactions may lead to novel strategies for controlling diseases like dengue and Zika.

Related Concept Videos

Yellow Fever01:18

Yellow Fever

Yellow fever is a viral hemorrhagic disease caused by the yellow fever virus (YFV), a member of the Flaviviridae family. It is transmitted primarily by Aedes and Haemagogus mosquitoes in tropical and subtropical regions of Africa and South America. After transmission through a mosquito bite, the virus initially replicates in skin-resident immune cells such as dendritic cells and macrophages. These cells then migrate to the lymph nodes, where viral replication increases, eventually leading to...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...