Genetics of Host Resistance to Retroviruses and Cancer

Okeoma, Chioma M.; Ross, Susan R.

doi:10.1007/978-0-387-09581-3_4

Cited by 3 publications

(3 citation statements)

References 143 publications

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“…It is unclear whether ERV-DCs are harmful or beneficial to the host. However, previous studies have indicated that the presence of other ERVs in vertebrates is associated with protection against infection of related exogenous retroviruses as well as with the generation of pathogenic viruses or tumors (9,25,28). Our studies further indicate that ERV-DC10 was not able to produce infectious particles when it was present in some cell types, including feline PBMCs (ERV-DC10 ϩ/ϩ genotype) and the feline fibroblast cell line AH927 (ERV-DC10 ϩ/ϩ ), suggesting that the ERV-DC10 promoter can be modified in a tissue-specific manner, similar to the endogenous human ERV syncytin (23), as expression of retroviral genes can be controlled by transcriptional modification (43).…”

Section: Discussionmentioning

confidence: 99%

Infectious Endogenous Retroviruses in Cats and Emergence of Recombinant Viruses

Anai

Ochi

Watanabe

et al. 2012

J Virol

189

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bEndogenous retroviruses (ERVs) comprise a significant percentage of the mammalian genome, and it is poorly understood whether they will remain as inactive genomes or emerge as infectious retroviruses. Although several types of ERVs are present in domestic cats, infectious ERVs have not been demonstrated. Here, we report a previously uncharacterized class of endogenous gammaretroviruses, termed ERV-DCs, that is present and hereditary in the domestic cat genome. We have characterized a subset of ERV-DC proviral clones, which are numbered according to their genomic insertions. One of these, ERV-DC10, located in the q12-q21 region on chromosome C1, is an infectious gammaretrovirus capable of infecting a broad range of cells, including human. Our studies indicate that ERV-DC10 entered the genome of domestic cats in the recent past and appeared to translocate to or reintegrate at a distinct locus as infectious ERV-DC18. Insertional polymorphism analysis revealed that 92 of 244 domestic cats had ERV-DC10 on a homozygous or heterozygous locus. ERV-DC-like sequences were found in primate and rodent genomes, suggesting that these ERVs, and recombinant viruses such as RD-114 and BaEV, originated from an ancestor of ERV-DC. We also found that a novel recombinant virus, feline leukemia virus subgroup D (FeLV-D), was generated by ERV-DC env transduction into feline leukemia virus in domestic cats. Our results indicate that ERV-DCs behave as donors and/or acceptors in the generation of infectious, recombinant viruses. The presence of such infectious endogenous retroviruses, which could be harmful or beneficial to the host, may affect veterinary medicine and public health.

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Section: Discussionmentioning

confidence: 99%

Infectious Endogenous Retroviruses in Cats and Emergence of Recombinant Viruses

Anai

Ochi

Watanabe

et al. 2012

J Virol

189

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“…There are other host genes that confer resistance or susceptibility to MMTV. These include MHC Class II genes required for efficient Sag presentation, the innate immune pathogen sensor toll-like receptor 4 ( Tlr 4), and several as-of-yet unidentified genes that affect the production of anti-MMTV antibodies or T cell responses to MMTV (reviewed in [ 43 ]). MMTV infection is also restricted by the intrinsic immune factor, apolipoprotein B editing complex 3 (APOBEC3) [ 44 ].…”

Section: Mmtv In Vivo Infectionmentioning

confidence: 99%

Mouse Mammary Tumor Virus Molecular Biology and Oncogenesis

Ross

2010

Viruses

Self Cite

103

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Mouse mammary tumor virus (MMTV), which was discovered as a milk-transmitted, infectious cancer-inducing agent in the 1930s, has been used since that time as an animal model for the study of human breast cancer. Like other complex retroviruses, MMTV encodes a number of accessory proteins that both facilitate infection and affect host immune response. In vivo, the virus predominantly infects lymphocytes and mammary epithelial cells. High level infection of mammary epithelial cells ensures efficient passage of virus to the next generation. It also results in mammary tumor induction, since the MMTV provirus integrates into the mammary epithelial cell genome during viral replication and activates cellular oncogene expression. Thus, mammary tumor induction is a by-product of the infection cycle. A number of important oncogenes have been discovered by carrying out MMTV integration site analysis, some of which may play a role in human breast cancer.

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“…The genomes of mammals and other species contain many genes that restrict pathogenic infectious retroviruses (Goff, 2004b; Harris et al, 2012; Malim and Bieniasz, 2012; Okeoma and Ross, 2010). Among these are the Apolipoprotein B Editing Complex 3 ( APOBEC3 ) genes, which have undergone positive selection and are present in different copy numbers in different species (Compton et al, 2012; OhAinle et al, 2006; Sawyer et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Nucleic Acid Recognition Orchestrates the Anti-Viral Response to Retroviruses

Stavrou

Blouch

Kotla

et al. 2015

Cell Host & Microbe

130

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SUMMARY Intrinsic restriction factors and viral nucleic-acid sensors are important for the anti-viral response. Here, we show how upstream sensing of retroviral reverse transcripts integrates with the downstream effector APOBEC3, an IFN-induced cytidine deaminase that introduces lethal mutations during retroviral reverse transcription. Using a Murine Leukemia Virus (MLV) variant with an unstable capsid that induces a strong IFNβ antiviral response, we identify three sensors, IFI203, DDX41 and cGAS, required for MLV nucleic-acid recognition. These sensors then signal using the adaptor STING, leading to increased production of IFNβ and other targets downstream of the transcription factor IRF3. Using knockout and mutant mice, we show that APOBEC3 limits the levels of reverse transcripts that trigger cytosolic sensing, and that nucleic-acid sensing in vivo increases expression of IFN-regulated restriction factors like APOBEC3 that in turn reduce viral load. These studies underscore the importance of the multiple layers of protection afforded by host factors.

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Genetics of Host Resistance to Retroviruses and Cancer

Cited by 3 publications

References 143 publications

Infectious Endogenous Retroviruses in Cats and Emergence of Recombinant Viruses

Infectious Endogenous Retroviruses in Cats and Emergence of Recombinant Viruses

Mouse Mammary Tumor Virus Molecular Biology and Oncogenesis

Nucleic Acid Recognition Orchestrates the Anti-Viral Response to Retroviruses

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