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2015 ; 126
(3
): 378-85
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Dengue virus binding and replication by platelets
#MMPMID25943787
Simon AY
; Sutherland MR
; Pryzdial EL
Blood
2015[Jul]; 126
(3
): 378-85
PMID25943787
show ga
Dengue virus (DENV) infection causes ?200 million cases of severe flulike illness
annually, escalating to life-threatening hemorrhagic fever or shock syndrome in
?500,000. Although thrombocytopenia is typical of both mild and severe diseases,
the mechanism triggering platelet reduction is incompletely understood. As a
probable initiating event, direct purified DENV-platelet binding was followed in
the current study by quantitative reverse transcription-polymerase chain reaction
and confirmed antigenically. Approximately 800 viruses specifically bound per
platelet at 37°C. Fewer sites were observed at 25°C, the blood bank storage
temperature (?350 sites), or 4°C, known to attenuate virus cell entry (?200
sites). Dendritic cell-specific intercellular adhesion molecule-3-grabbing
nonintegrin (DC-SIGN) and heparan sulfate proteoglycan were implicated as
coreceptors because only the combination of anti-DC-SIGN and low-molecular-weight
heparin prevented binding. Interestingly, at 37°C and 25°C, platelets replicated
the positive sense single-stranded RNA genome of DENV by up to ?4-fold over 7
days. Further time course experiments demonstrated production of viral NS1
protein, which is known to be highly antigenic in patient serum. The infectivity
of DENV intrinsically decayed in vitro, which was moderated by platelet-mediated
generation of viable progeny. This was shown using a transcription inhibitor and
confirmed by freeze-denatured platelets being incapable of replicating the DENV
genome. For the first time, these data demonstrate that platelets directly bind
DENV saturably and produce infectious virus. Thus, expression of antigen encoded
by DENV is a novel consideration in the pathogen-induced thrombocytopenia
mechanism. These results furthermore draw attention to the possibility that
platelets may produce permissive RNA viruses in addition to DENV.
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