For COVID-19 vaccine updates, please review our information guide. For patient eligibility and scheduling availability, please visit VaccineTogetherNY.org.

Variation in adenovirus transgene expression between BALB/c and C57BL/6 mice is associated with differences in interleukin-12 and gamma interferon production and NK cell activation.

TitleVariation in adenovirus transgene expression between BALB/c and C57BL/6 mice is associated with differences in interleukin-12 and gamma interferon production and NK cell activation.
Publication TypeJournal Article
Year of Publication2001
AuthorsPeng Y, Falck-Pedersen E, Elkon KB
JournalJ Virol
Volume75
Issue10
Pagination4540-50
Date Published2001 May
ISSN0022-538X
KeywordsAdenoviruses, Human, Animals, CD8-Positive T-Lymphocytes, Cell Line, Defective Viruses, Gene Expression, Genetic Vectors, Humans, Interferon-gamma, Interleukin-12, Killer Cells, Natural, Liver, Lymphocyte Activation, Lymphocyte Depletion, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Transgenes
Abstract

The innate immune response against replication-defective adenoviruses (Ad) is poorly defined. We and others have previously observed striking differences in the rate at which the Ad vector itself or the virus encoding a variety of transgenes is eliminated in different mouse strains. Here, we report that Ad infection of BALB/ mice is associated with sixfold-higher levels of serum alanine aminotransferase and that Ad transgenes induce two- to threefold-higher levels of intrahepatic NK cells and NK activity compared to C57BL/6 mice. The increase in NK activation in BALB/c mice was associated with approximately 4-fold higher level of mRNA expression of a newly described NKG2 receptor activator, H-60, as well as increased expression of interleukin-12 and gamma interferon mRNAs in BALB/c mice compared to C57BL/6 mice. NK depletion in BALB/c mice or defective NK function in C3H beige mice extended transgene expression compared to their appropriate controls, and attenuation of NK together with CD8 T-cell function had a synergistic effect. These findings indicate that there are intrinsic differences in the innate immune responses of different mouse strains to Ad and Ad transgenes and that NK cells, in cooperation with CD8 T cells, play a pivotal role in the early extinction of transgene expression in BALB/c mice.

DOI10.1128/JVI.75.10.4540-4550.2001
Alternate JournalJ Virol
PubMed ID11312324
PubMed Central IDPMC114207
Grant ListHL-9308-L / HL / NHLBI NIH HHS / United States

Weill Cornell Medicine Microbiology and Immunology 1300 York Avenue, Box 62 New York, NY 10065 Phone: (212) 746-6505 Fax: (212) 746-8587