4.6 Article

Negeviruses Reduce Replication of Alphaviruses during Coinfection

Journal

JOURNAL OF VIROLOGY
Volume 95, Issue 14, Pages -

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00433-21

Keywords

Negev virus; alphavirus; insect-specific virus; negevirus; paratransgenesis; superinfection exclusion

Categories

Funding

  1. Liverpool School of Tropical Medicine Director's Catalyst Fund award
  2. NIH [R01-AI095753-01A1, R01-AI125902, R21AI138074]
  3. BBSRC [BB/T001240/1, V011278/1]
  4. Royal Society Wolfson Fellowship [RSWF\R1\180013]
  5. NIHR [NIHR2000907]
  6. URKI [20197]
  7. BBSRC [BB/T001240/1] Funding Source: UKRI

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Negeviruses can reduce the replication of alphaviruses in mosquito cells and further inhibit CHIKV replication by expressing anti-CHIKV antibody fragments. This demonstrates their potential for controlling arthropod-borne pathogens.
Negeviruses are a group of insect-specific viruses (ISVs) that have been found in many arthropods. Their presence in important vector species led us to examine their interactions with arboviruses during coinfections. Wild-type negeviruses reduced the replication of several alphaviruses during coinfections in mosquito cells. Negev virus (NEGV) isolates were also used to express green fluorescent protein (GFP) and anti-chikungunya virus (CHIKV) antibody fragments during coinfections with CHIKV. NEGV expressing anti-CHIKV antibody fragments was able to further reduce replication of CHIKV during coinfections, while reductions of CHIKV with NEGV expressing GFP were similar to titers with wild-type NEGV alone. These results are the first to show that negeviruses induce superinfection exclusion of arboviruses and to demonstrate a novel approach to deliver antiviral antibody fragments with paratransgenic ISVs. The ability to inhibit arbovirus replication and express exogenous proteins in mosquito cells makes negeviruses a promising platform for control of arthropod-borne pathogens. IMPORTANCE Negeviruses are a group of insect-specific viruses (ISVs), viruses known to infect only insects. They have been discovered over a wide geographical and species range. Their ability to infect mosquito species that transmit dangerous arboviruses makes negeviruses a candidate for a pathogen control platform. Coinfections of mosquito cells with a negevirus and an alphavirus demonstrated that negeviruses can inhibit the replication of alphaviruses. Additionally, modifying Negev virus (NEGV) to express a fragment of an anti-CHIKV antibody further reduced the replication of CHIKV in coinfected cells. This is the first evidence to demonstrate that negeviruses can inhibit the replication of important arboviruses in mosquito cells. The ability of a modified NEGV to drive the expression of antiviral proteins also highlights a method for negeviruses to target specific pathogens and limit the incidence of vector-borne diseases.

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