INSTITUTO DE BIOTECNOLOGIA Y BIOLOGIA MOLECULAR
Unidad Ejecutora - UE
congresos y reuniones científicas
Platelets control CVB3 infection in vivo
JAQUENOD DE GIUSTI, CAROLINA; ALBERDI, LUCRECIA; SCHARRIG, EMILIA; RIVADENEYRA, LEONARDO; GOMEZ, RICARDO M.; SCHATTNER, MIRTA
Congreso; XXIV Congress of the International Society of Thrombosis and Haemostasis; 2013
International Society of Thrombosis and Haemostasis
Background: It has been recently demonstrated that mice profoundly depleted of platelets (>95% depletion) and infected with the LCMV Armstrong strain developed hemorrhagic spots in several organs along with high viral titers and increased mortality. Interestingly, the presence of 15% of platelets (partial depletion) was sufficient to prevent vascular damage but not viral replication. These observations not only confirm the novel notion that platelets are necessary to protect vascular integrity and are critical mediators of viral clearance, but also underscore an underappreciated relationship between platelet-mediated hemostasis, and viral infection. Aim: To examine whether this novel function of platelets is specifically related to a murine pathogen as LCMV, or if it is also present during other viral infections and using a human virus. Methods: C57BL/6 male mice 5 weeks old were inoculated intraperitonally (IP) with PBS or with 30 µl of a specific polyclonal antiserum against platelets diluted 1:4 in PBS every 48 hs. One day after the first injection, groups of mice (4-8) were infected IP with 1x104 UFP of a myocarditic variant of Coxsackievirus B3 (CVB3), or 1x104 UFP of the LCMV, Armstrong strain used as positive control. Platelet-depleted and non-depleted non-infected animals were used as negative controls. After 14 days post infection (dpi) survived animals were sacrificed and heart or spleen tissues from CVB3 or LCMV-infected animals respectively, tested for the presence for infectivity of virus by plaque assay as well as for histopathology. Results: The platelet antiserum treatment produced 92% of platelet depletion at 4h, 86% at 24h and 78% at 48 h post-treatment. At 6 dpi, mortality was 25% in CVB3-infected and 50% in CVB3-infected and depleted mice. No further deaths were observed after 6dpi or in depleted uninfected animals. Infectivity assays of homogenates of heart tissues from CVB3-infected mice were 25% positive (1/4) and the only positive show approximately 10 UFP/mg of tissue. In contrast, in CVB3-infected and platelet depleted mice showed 100% (4/4) infectivity ranging 1x10 to 102 UFP/mg of heart tissues. Analysis of histopathology showed typical multifocal acute myocarditis in all infected animals. However, the number and the extent of the lesions were approximately double in hearts of infected and depleted animals. In agreement with previously published results, infectious LCMV was detected only in the spleen of LCMV-infected and depleted animals. Bleeding was not observed in any group. Summary/conclusions: Our results indicate that murine platelets have a role in controlling viral infection not only for the murine pathogen LCMV but also for a human pathogen as CVB3. This uncontrolled viral infection results in a more severe pathology.