| 1. |
- Hurwitz, Julia L., et al.
(författare)
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Hypothesis : RNA and DNA Viral Sequence Integration into the Mammalian Host Genome Supports Long-Term B Cell and T Cell Adaptive Immunity
- 2017
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Ingår i: Viral immunology. - : MARY ANN LIEBERT, INC. - 0882-8245 .- 1557-8976. ; 30:9, s. 628-632
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Viral sequence integration into the mammalian genome has long been perceived as a health risk. In some cases, integration translates to chronic viral infection, and in other instances, oncogenic gene mutations occur. However, research also shows that animal cells can benefit from integrated viral sequences (e.g., to support host cell development or to silence foreign invaders). Here we propose that, comparable with the clustered regularly interspaced short palindromic repeats that provide bacteria with adaptive immunity against invasive bacteriophages, animal cells may co-opt integrated viral sequences to support immune memory. We hypothesize that host cells express viral peptides from open reading frames in integrated sequences to boost adaptive B cell and T cell responses long after replicating viruses are cleared. In support of this hypothesis, we examine previous literature describing (1) viruses that infect acutely (e.g., vaccinia viruses and orthomyxoviruses) followed by unexplained, long-term persistence of viral nucleotide sequences, viral peptides, and virus-specific adaptive immunity, (2) the high frequency of endogenous viral genetic elements found in animal genomes, and (3) mechanisms with which animal host machinery supports foreign sequence integration.
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| 2. |
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| 3. |
- Lind, Alexander, et al.
(författare)
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Antibody Affinity Against 2009 A/H1N1 Influenza and Pandemrix Vaccine Nucleoproteins Differs Between Childhood Narcolepsy Patients and Controls
- 2017
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Ingår i: Viral immunology. - : Mary Ann Liebert Inc. - 0882-8245 .- 1557-8976. ; 30:8, s. 590-600
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Tidskriftsartikel (refereegranskat)abstract
- Increased narcolepsy incidence was observed in Sweden following the 2009 influenza vaccination with Pandemrix((R)). A substitution of the 2009 nucleoprotein for the 1934 variant has been implicated in narcolepsy development. The aims were to determine (a) antibody levels toward wild-type A/H1N1-2009[A/California/04/2009(H1N1)] (NP-CA2009) and Pandemrix-[A/Puerto Rico/8/1934(H1N1)] (NP-PR1934) nucleoproteins in 43 patients and 64 age-matched controls; (b) antibody affinity in reciprocal competitive assays in 11 childhood narcolepsy patients compared with 21 age-matched controls; and (c) antibody levels toward wild-type A/H1N1-2009[A/California/04/2009(H1N1)] (H1N1 NS1), not a component of the Pandemrix vaccine. In vitro transcribed and translated S-35-methionine-labeled H1N1 influenza A virus proteins were used in radiobinding reciprocal competition assays to estimate antibody levels and affinity (Kd). Childhood patients had higher NP-CA2009 (p=0.0339) and NP-PR1934 (p=0.0246) antibody levels compared with age-matched controls. These childhood controls had lower NP-CA2009 (p=0.0221) and NP-PR1934 (p=0.00619) antibodies compared with controls 13 years or older. In contrast, in patients 13 years or older, the levels of NP-PR1934 (p=0.279) and NP-CA2009 (p=0.0644) antibodies did not differ from the older controls. Childhood antibody affinity (Kd) against NP-CA2009 was comparable between controls (68ng/mL) and patients (74ng/mL; p=0.21) with NP-CA2009 and NP-PR1934 displacement (controls: 165ng/mL; patients: 199ng/mL; p=0.48). In contrast, antibody affinity against NP-PR1934 was higher in controls with either NP-PR1934 (controls: 9ng/mL; patients: 20ng/mL; p=0.0031) or NP-CA2009 (controls: 14ng/mL; patients: 23ng/mL; p=0.0048). A/H1N1-NS1 antibodies were detected in 0/43 of the narcolepsy patients compared with 3/64 (4.7%) controls (p=0.272). Similarly, none (0/11) of the childhood patients and 1/21 (4.8%) of the childhood controls had A/H1N1-NS1 antibodies. The higher antibody affinities against NP-PR1934 in controls suggest better protection against wild-type virus. In contrast, the reduced NP-PR1934 antibody affinities among childhood narcolepsy patients suggest poor protection from the wild-type A/H1N1 virus and possibly increased risk for viral damage.
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| 4. |
- Niklasson, Bo, et al.
(författare)
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Diabetes Prevention Through Antiviral Treatment in Biobreeding Rats
- 2016
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Ingår i: Viral immunology. - : Mary Ann Liebert Inc. - 0882-8245 .- 1557-8976. ; 29:8, s. 452-458
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Tidskriftsartikel (refereegranskat)abstract
- A picornavirus (Ljungan virus) has been associated with diabetes in its wild rodent reservoir and in diabetesprone biobreeding (DP-BB) rats. We attempted to alter the development of diabetes in DP-BB rats using two anti-picornavirus compounds (pleconaril and APO-N039), singly or in combination. Antiviral therapy was initiated 2 weeks before expected onset of diabetes. Pleconaril or APO-N039 alone did not affect the debut of diabetes. However, animals receiving a combination of both compounds were protected for at least the entire period of treatment (4 weeks after expected time of diabetes onset). Immunohistochemistry demonstrated that the presence and distribution of virus antigen in the pancreatic islets coincided with the clinical status of the animal. Data indicate that a treatable picornavirus can be involved in the cellular assault resulting in diabetes and in these cases the disease mechanism appears to involve a virus present in the pancreatic beta cell mass itself.
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