No major change in vCJD agent strain after secondary transmission via blood transfusion

Abstract

Background: The identification of transmission of variant Creutzfeldt-Jakob disease (vCJD) by blood transfusion has prompted investigation to establish whether there has been any alteration in the vCJD agent following this route of secondary transmission. Any increase in virulence or host adaptation would require a reassessment of the risk analyses relating to the possibility of a significant secondary outbreak of vCJD. Since there are likely to be carriers of the vCJD agent in the general population, there is a potential for further infection by routes such as blood transfusion or contaminated surgical instruments.

Methodology: We inoculated both wild-type and transgenic mice with material from the first case of transfusion associated vCJD infection.

Principal findings: The strain transmission properties of blood transfusion associated vCJD infection show remarkable similarities to the strain of vCJD associated with transmission from bovine spongiform encephalopathy (BSE).

Conclusions: Although it has been hypothesized that adaptation of the BSE agent through secondary passage in humans may result in a greater risk of onward transmission due to an increased virulence of the agent for humans, our data presented here in two murine models suggest no significant alterations to transmission efficiency of the agent following human-to-human transmission of vCJD.

Figure 1. Comparison of incubation periods in wild-type mice.

Incubation period plot comparison of vCJD (transfusion) case versus transmissions in wild-type mice of vCJD (BSE) from three sources. (Data shows mean incubation period±standard error of the mean. Open circles RIII line and open triangles VM line.)

Figure 2. Vacuolation scoring in the mouse brain.

Lesion profile comparison of vCJD (transfusion) case versus vCJD (BSE) transmissions to identify similarities in vacuolar pathology levels and regional distribution in mouse brains. (mean score ±SEM; dashed line - vCJD (transfusion) case; solid lines – 3x vCJD (BSE) cases for wild-type mice (diamonds – vCJD(BSE) A; squares – vCJD(BSE) B; triangles – vCJD(BSE) C) and published vCJD (BSE) for HuMM transgenic; G1–G9 grey matter scoring regions; W1–W3 white matter scoring regions)

Figure 3. Detection of abnormal PrP in the mouse brain.

Immunocytochemical detection of abnormal PrP deposition in hippocampus and thalamus (lateral posterior nucleus) of HuMM transgenic (with additional 40× magnification of florid plaque structure, see box lower left) and VM wild-type mice following inoculation with vCJD (BSE) and vCJD (transfusion) material. (Scale bar 200 µm, anti-PrP antibody 6H4)

Figure 4. PrP^Sc typing by Western blot.

Brain homogenates from HuMM mice inoculated with both vCJD (BSE) and vCJD (transfusion) show similar mobility and glycosylation profile (type 2B) as material from vCJD patients. (T2B: control vCJD material; antibody: 6H4)