Calicivirus (genus Vesivirus)
associated with post-transfusion
hepatitis
Smith AW, Kurth A, Skilling DE, Smith CC, Iversen PL,
Bok K, Matson DO
Oregon State University (AWS, DES); Laboratory for Calicivirus
Studies (AWS, DES, CCS); Robert Koch Institute (AK); AVI
BioPharma (PLI); National Institutes of Allergy and Infectious
Disease (KB); East Virginia Medical School (KB, DOM)
Electron photomicrograph of Cetacean
calicivirus showing typical morphology.
Negative stain. Bar equals 100nm. Photo by Douglas E. Skilling.
Cryomicroscopy by BV Prasad
Genera (four) within the family Caliciviridae
•
•
•
•
Norovirus
Lagovirus
Sapovirus
Vesivirus
1. Feline calicivirus
2. Marine caliciviruses
• Vesicular exanthema of swine (13)
• San Miguel Sea-lion virus (17)
• Cetacean, Bovine, Reptile, Primate, rabbit, walrus etc. (>10)
Evidence of diseases seen in association
with caliciviruses (genus vesivirus) in
phylogenetically diverse animal species.
Disease condition
Blisters
Hepatitis
Diarrhea
Abortion
Encephalitis
Pneumonia
Hemorrhage
Myocarditis
Pancreatitis
Swine
Seal
Cat
Cattle
Human
Primate
Dog
Snake
Whale
Horse
Rabbit
OVERVIEW
• What is a Vesivirus ?
• Brief History
• Diseases caused by Vesivirus
• Hepatitis and the Blood Supply
• Conclusions
• Acknowledgments
Calicivirus Antibody in Human Blood
Red Cross & Clinical Samples
(cut point 0.043 OD)
Groups
Pos / N
% Positive
Red Cross
Normal N=374
44/374
12%
Red Cross
> ALT N=350
73/350
21%
Hepatitis
Clinical
12/41
29%
Post Trans
Hepatitis
7/15
47%
1. Humans are routinely exposed to calicivirus
2. Significant Association between Hepatitis and Calicivirus anitbody
3. Donor blood can contain Calicivirus
4. Calicivirus Hepatitis can likely be Blood Transmitted
P-value v.
Normal
< 0.001
< 0.001
Viremic Red Cross Donor Samples that were
normal, had elevated ALT levels or were
ELISA Positive (11 / 108)
Human Sera, Red Cross, Oregon
Sera @ 1:100 Dilution (cut point 0.100 OD)
97/703
Positive to CsCl 5, 13, 17
=
12.37%
20/703
Positive to Hepatitis E
=
2.84%
1/703
Positive to SMSV-9
=
0.14%
20/703
Positive to F-9
=
2.84%
Human Sera, Red Cross, Oregon
Normal Sera (374)
Human Sera, Red Cross, Oregon
Elevated Alt Sera (329)
33/374
Positive to CsCl 5, 13, 17
=
8.82%
54/329
Positive to CsCl 5, 13, 17
=
16.41%
4/374
Positive to CsCl 5, 13, 17 & F-9
=
1.06%
5/329
Positive to CsCl 5, 13, 17 & F-9
=
1.51%
1/374
Positive to CsCl 5, 13, 17 & HEV
=
0.26%
3/329
Positive to CsCl 5, 13, 17 & HEV
=
0.91%
9/374
Positive to F-9
=
2.40%
11/329
Positive to F-9
=
3.34%
9/374
Positive to HEV
=
2.40%
11/329
Positive to HEV
=
3.34%
1/374
Positive to SMSV-9
=
0.26%
0/329
Positive to SMSV-9
=
0%
0/374
Positive to F-9 & HEV
=
0%
0/329
Positive to F-9 & HEV
=
0%
0/374
Positive to SMSV-9 and other
types
=
0%
0/329
Positive to SMSV-9 and other
types
=
0%
ELISA at 1:100
Serum dil. Using
CsCl antg. 5,13,17
compared to D3A
and 7420
U.S. Normal Donors
and Three
Transmission
Associated Hepatitis
Donors
Source CH-ON
Positive = OD > 0.100
Mean Corrected OD
ELISA at 1:100 Serum dil. Using CsCl antg. 5, 13, 17. Compared
to D3A and 7420 in Italian Normal Blood Donors
Source CH-ON
Serum #
LCS
CH-ON
History
OD-minus
Serum
Cont
Correct OD
D3A
7420
11
1
Normal Donor
0.064
0.008
0.056
0.031
0.024
12
2
Normal Donor
0.006
0.000
0.006
0.024
0.031
13
3
Normal Donor
0.010
0.000
0.010
0.025
0.046
14
4
Normal Donor
0.000
0.000
0.000
0.009
0.019
15
5
Normal Donor
0.018
0.013
0.005
0.092
0.036
Positive OD > 0.100
0/5
=0%
0/5=0%
0/5=0%
Mean Corrected OD
0.015
0.036
0.031
ELISA at 1:100 Serum dil. Using CsCl antg. 5, 13, 17. Compared
to D3A and 7420. Italian Samples Positive for HBV or HCV
Source CH-ON
Serum #
LCS
CH-ON
History
OD-minus
Serum Cont
Correct OD
D3A
7420
1
29
HCV+
0.009
0.004
0.005
0.009
.016
2
30
HCV+
0.245
0.106
0.139
0.034
.082
3
31
HCV+
0.004
0.002
0.002
0.052
.118
4
32
HCV+
0.001
0.004
-0.003
0.015
.053
5
33
HCV+
0.033
0.014
0.019
6
1
HBV+
0.011
0.001
0.010
0.027
.051
7
2
HBV+
0.002
0.000
0.002
0.038
.103
8
3
HBV+
0.032
0.000
0.032
0.091
.082
9
4
HBV+
0.157
0.000
0.157
0.233
10
7
HBV+
0.035
0.000
0.035
0.058
.017
OD > 0.100
2/10
=20%
1/9
=12%
2/8
=25%
Mean Corrected OD
0.040
0.062
0.067
ELISA at 1:100 Serum dil. Using CsCl antg.5,13,17. Compared
to D3A and 7420 Italy Cryptogenic Hepatitis Non A-G Negative
Source CH-ON
Serum #
LCS
CH-ON
History
OD-minus
Serum Cont
Correct OD
D3A
7420
16
52
Hepatitis
0.057
0.029
0.028
0.159
0.239
17
53
Hepatitis
0.110
0.045
0.065
0.110
0.183
18
54
Hepatitis
0.017
0.008
0.009
0.091
0.082
19
55
Hepatitis
0.134
0.010
0.124
0.220
20
56
Hepatitis
0.028
0.018
0.010
0.032
0.144
21
57
Hepatitis
0.012
0.004
0.008
0.026
0.024
22
60
Hepatitis
0.022
0.015
0.007
0.016
0.025
23
61
Hepatitis
0.123
0.007
0.116
0.082
0.054
24
62
Hepatitis
0.018
0.005
0.013
0.067
0.264
25
63
Hepatitis
0.020
0.010
0.010
0.080
0.125
26
64
Hepatitis
0.066
0.023
0.043
0.355
0.617
27
65
Hepatitis
0.028
0.006
0.022
0.093
0.156
28
66
Hepatitis
0.077
0.000
0.077
0.146
0.034
29
67
Hepatitis
0.082
0.070
0.012
0.116
0.140
30
68
Hepatitis
0.009
0.006
0.003
0.058
0.089
31
69
Hepatitis
0.016
0.009
0.007
0.118
0.077
Positive OD > 0.100
2/16
=12%
6/16
=38%
8/15
=53%
Mean Corrected OD
0.035
0.110
0.150
ELISA at 1:100 Serum dil.
Using CsCl antg. 5, 13, 17.
Compared to D3A
and 7420 (Spain) PostTransfusion Hepatitis and
Elevated ALT
(U.S.) Post-Transfusion
Hepatitis and Post-Dialysis
Source CH-ON
Positive = OD > 0.100
Mean Corrected OD
*Serial Samples from 2 patients
** Western Blot positive SMSV-17 antg from the pool