Simian Varicella Virus Pathogenesis in Skin during Varicella and Zoster
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethis Statement
2.2. Monkeys
2.3. Acute SVV Infection and Establishment of Latency
2.4. Immunosuppressive Regimens
2.5. Determination of Anti-SVV Antibody Levels
2.6. Collection and Analysis of Blood Samples for SVV DNA by qPCR
2.7. DNA Extractions from Skin Scrapings and qPCR Analysis
2.8. Harvesting and Processing of Skin Samples for Immunohistochemistry
2.9. Immunohistochemistry
3. Results
3.1. Primary SVV Infection in Rhesus Macaques, Establishment of Latency, and Immunosuppression
3.2. Skin Rash during Varicella and Zoster
3.3. Detection of SVV DNA in Skin Scrapings during Varicella
3.4. Detection of SVV DNA in PBMCs during Varicella and Immunosuppression
3.5. SVV-Specific Antibody Response during Varicella and Zoster
3.6. Detection of SVV DNA in Skin Scrapings during Zoster
3.7. Detection of SVV Antigens in Skin and Colocalization of SVV Antigens with a Neuronal Marker during Varicella and Zoster
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Group | Monkey ID | Age a | Sex | Weight (Kg) | Primary Infection (dpi b) | Reactivation | |
---|---|---|---|---|---|---|---|
Treatment | Dpx c/mpi d | ||||||
1 | KI92 | 4.0 | M | 9.9 | 7 | A e | 84 |
KG58 | 4.2 | M | 9.5 | 9 | A | 63 | |
2 | LB56 | 6.7 | M | 8.2 | 9 | B f | 45 |
LT26 | 4.3 | M | 4.3 | 9 | B | 66 | |
LK67 | 4.7 | M | 8.1 | 9 | B | 42 | |
LR16 | 4.4 | M | 8.3 | 9 | B | 10 | |
LR42 | 4.4 | M | 8.0 | 9 | B | 56 | |
LR70 | 4.4 | M | 9.2 | 9 | B | 45 | |
3 | LT27 | 4.3 | M | 8.3 | 9 | C g | 3.8 d |
LE91 | 6.6 | M | 10.5 | 7 | C | - | |
control | B321 | 3.0 | M | 5.9 | D h | E i | 56 |
control | R110368 | 5.0 | M | U j | NA k | NA | NA |
Group | Monkey ID | Severity a | SVV ORF 61 DNA (Copy #/100 ng) |
---|---|---|---|
1 | KI92 | 2+ | NA b |
KG58 | 4+ | NA | |
2 | LB56 | 3+ | 50 |
LT26 | 4+ | 5 × 105 | |
LK67 | 4+ | 1 × 106 | |
LR16 | 3+ | 310 | |
LR42 | 2+ | 6 × 104 | |
LR70 | 4+ | 2 × 103 | |
3 | LT27 | 4+ | 1 × 107 |
LE91 | 2+ | 4 × 105 |
Group | Monkey ID | SVV ORF 61 DNA Copy #/100 ng a | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Days Post-Inoculation | ||||||||||
4 | 7 | 9/10 | 11 | 14 | 21 | 29/30 | 42 | 64 | ||
1 | KI92 | 26 | 4 | 6 | 20 | 0 | 0 | 0 | NA b | 1 |
KG58 | 78 | 161 | 20 | 12 | 2 | 1 | 0 | NA | 3 | |
2 | LB56 | 0 | 95 | 0 | NA | 0 | 0 | 0 | 0 | 0 |
LT26 | 21 | 103 | 9 | NA | 0 | 0 | 0 | 0 | 0 | |
LK67 | 0 | 103 | 31 | NA | 9 | 17 | 6 | 0 | 0 | |
LR16 | 7 | 36 | 8 | NA | 0 | 0 | 0 | 0 | 0 | |
LR42 | 7 | 282 | 40 | NA | 7 | 3 | 0 | 0 | 0 | |
LR70 | 21 | 128 | 16 | NA | 0 | 0 | 0 | 0 | 0 | |
3 | LT27 | 0 | 414 | 47 | NA | 0 | 0 | 0 | 0 | 0 |
LE91 | 0 | 23 | 0 | NA | 0 | 0 | 0 | 0 | 0 |
Group | Monkey ID | SVV ORF 61 DNA Copy #/100 ng a | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Days Post-Immunosuppression Treatment (dpx) | ||||||||||||||
Pre | 5/7 | 12/14 | 19/21 | 28 | 35 | 42 | 49 | 56 | 63 | 70 | 84 | 112 | ||
1 | KI92 | 0 | 0 | 0 | 2 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | NA b |
KG58 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | NA | |
2 | LB56 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | NA | 0 | 0 | 0 |
LT26 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
LK67 | 0 | 0 | 0 | 8 | 3 | 0 | 0 | 6 | 0 | NA | 0 | 0 | 0 | |
LR16 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | NA | 0 | 0 | NA | |
LR42 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 3 | |
LR70 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | NA | 0 | 2 | 3 | |
Months post infection (mpi) | ||||||||||||||
2 | 2.2 | 2.4 | 2.6 | 3 | 3.2 | 3.4 | 3.6 | 3.8 | 4.1 | 4.3 | 4.8 | 5.7 | ||
3 | LT27 c | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 7 | 0 | 0 | 0 | 4 | 0 |
LE91 c | 0 | 0 | 0 | 6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 |
Group | Monkey ID | Anti-SVV Antibody Titer a | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
PRE | Dpi b | Dpx c | Necropsy | |||||||
14 | 28 | 70 | 14 | 42 | 56 | 70 | ||||
1 | KI92 | <1:10 | 1:160 | 1:160 | 1:320 | 1:40 | 1:80 | NA d | 1:40 | 1:40 |
KG58 | <1:10 | 1:160 | 1:160 | 1:320 | 1:160 | 1:160 | NA | 1:40 | 1:80 | |
2 | LB56 | <1:10 | 1:160 | 1:160 | 1:160 | 1:160 | 1:80 | 1:320 | 1:160 | 1:320 |
LT26 | <1:10 | 1:160 | 1:160 | 1:640 | 1:320 | 1:320 | 1:640 | 1:320 | 1:640 | |
LK67 | <1:10 | 1:160 | 1:80 | 1:80 | 1:80 | 1:160 | 1:160 | 1:80 | 1:160 | |
LR16 | <1:10 | 1:160 | 1:80 | 1:160 | 1:80 | 1:80 | 1:160 | 1:80 | 1:160 | |
LR42 | <1:10 | 1:320 | 1:320 | 1:160 | 1:320 | 1:320 | 1:320 | 1:160 | 1:320 | |
LR70 | <1:10 | 1:160 | 1:80 | 1:160 | 1:160 | 1:160 | 1:160 | 1:160 | 1:320 | |
Months post inoculation (mpi) | ||||||||||
PRE | 0.5 | 1.0 | 2.3 | 2.5 | 3.4 | 3.8 | 4.3 | 8.0 | ||
3 | LT27 e | <1:10 | 1:320 | 1:320 | 1:160 | 1:320 | 1:160 | 1:80 f | 1:80 | 1:1280 |
LE91 e | <1:10 | 1:80 | 1:40 | 1:20 | 1:40 | 1:20 | 1:40 | 1:20 | 1:40 |
Group | Monkey ID | SVV ORF 61 DNA Copy #/100 ng a | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Days Post-Reactivation (dpx) | |||||||||||
10 | 42 | 45 | 49 | 56 b | 63 | 66 b | 70 | 91 | 107 | ||
1 | KI92 | 127 | |||||||||
2 | LB56 | 1 | 6 | 16, 9 | |||||||
LT26 | 1, 6 | ||||||||||
LK67 | 2 | 3 | 5 | ||||||||
LR16 | 6 | 4 | |||||||||
LR42 | 2 | 12 | 38 | ||||||||
LR70 | 3 | ||||||||||
Months post inoculation (mpi) | |||||||||||
3.8 | |||||||||||
3 | LT27 c | 10 |
Monkey ID | Uninfected | Pre- infection | Acute Infection (dpi) | Reactivation (dpx/mpi a) | Antiserum | |||
---|---|---|---|---|---|---|---|---|
Group | SVV IE 63 | SVV Nucleo-Capsid | ß-III Tubulin | |||||
R110368 | SVV- b | NR c | NR | - | - | + | ||
1 | KI92 | NA d | 91 | + | + | + | ||
KG58 | NA | 107 | + | + | + | |||
2 | LB56 | SVV- | - e | - | + | |||
9 | + | - | + | |||||
45 | + | + | + | |||||
49 | + | - | + | |||||
56 | + | - | + | |||||
LK67 | SVV- | - | - | + | ||||
9 | + | - | + | |||||
42 | + | + | + | |||||
49 | NA | NA | NA | |||||
70 | NA | NA | NA | |||||
LR16 | SVV- | - | - | + | ||||
9 | + | - | + | |||||
10 | + | + | + | |||||
45 | NA | NA | NA | |||||
LR42 | SVV- | - | - | + | ||||
9 | + | + | + | |||||
56 | + | - | + | |||||
63 | + | + | + | |||||
70 | + | + | + | |||||
LR70 | SVV- | - | - | + | ||||
9 | + | - | + | |||||
45 | + | + | + | |||||
3 | LT27 | SVV- | - | - | + | |||
9 | + | + | - | |||||
3.8 a | + | + | + |
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Mahalingam, R.; Feia, B.; Coleman, C.; Anupindi, K.; Saravanan, P.; Luthens, A.; Bustillos, A.; Das, A.; de Haro, E.; Doyle-Meyers, L.; et al. Simian Varicella Virus Pathogenesis in Skin during Varicella and Zoster. Viruses 2022, 14, 1167. https://doi.org/10.3390/v14061167
Mahalingam R, Feia B, Coleman C, Anupindi K, Saravanan P, Luthens A, Bustillos A, Das A, de Haro E, Doyle-Meyers L, et al. Simian Varicella Virus Pathogenesis in Skin during Varicella and Zoster. Viruses. 2022; 14(6):1167. https://doi.org/10.3390/v14061167
Chicago/Turabian StyleMahalingam, Ravi, Brittany Feia, Colin Coleman, Kusala Anupindi, Pratush Saravanan, Amalia Luthens, Amalia Bustillos, Arpita Das, Eileen de Haro, Lara Doyle-Meyers, and et al. 2022. "Simian Varicella Virus Pathogenesis in Skin during Varicella and Zoster" Viruses 14, no. 6: 1167. https://doi.org/10.3390/v14061167
APA StyleMahalingam, R., Feia, B., Coleman, C., Anupindi, K., Saravanan, P., Luthens, A., Bustillos, A., Das, A., de Haro, E., Doyle-Meyers, L., Looper, J., Bubak, A. N., Niemeyer, C. S., Palmer, B., Nagel, M. A., & Traina-Dorge, V. (2022). Simian Varicella Virus Pathogenesis in Skin during Varicella and Zoster. Viruses, 14(6), 1167. https://doi.org/10.3390/v14061167