Negeviruses Reduce Replication of Alphaviruses during Coinfection
...
Patterson, Edward Ian | 2021
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.
LEER