Can viruses do good things?

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Can viruses be beneficial? Did they aid the development of life on this planet? Can they be used in treating cancer? Can they protect plants against drought and cold temperatures? Can they protect against infection? Are they, in fact, essential for life on Earth? See the background and the research …

**updated 2021**

Background:

*Nuwer, R. (2020). Why the world needs viruses to function. BBC Future.

*Quammen, D. (2021). How viruses shape our world: COVID-19 is a reminder of their destructive power, but they’re crucial to humans’ development and survival. National Geographic.

Featured articles (these articles have been added to the Science Primary Literature database):

*Alemany, R. (2013). Viruses in cancer treatment. Clinical & Translational Oncology, 15(3), 182-188. [Cited by]

“Soon after the discovery that viruses cause human disease, started the idea of using viruses to treat cancer. After the initial indiscriminate use, crude preparations of each novel virus in the early twentieth century, a second wave of virotherapy blossomed in the 1960s with purified and selected viruses. Responses were rare and short-lived. Immune rejection of the oncolytic viruses was identified as the major problem and virotherapy was abandoned. During the past two decades, virotherapy has re-emerged with engineered viruses, with a trend towards using them as tumor-debulking immunostimulatory agents combined with radio or chemotherapy. Currently, oncolytic Reovirus, Herpes, and Vaccinia virus are in late phase clinical trials. Despite the renewed hope, efficacy will require improving systemic tumor targeting, overcoming stroma barriers for virus spread, and selectively stimulating immune responses against tumor antigens but not against the virus. Virotherapy history, viruses, considerations for clinical trials, and hurdles are briefly overviewed.”

*Cattaneo, R., Miest, T., Shashkova, E. V., & Barry, M. A. (2008). Reprogrammed viruses as cancer therapeutics: Targeted, armed and shielded. Nature Reviews. Microbiology, 6(7), 529-540. [PDF] [Cited by]

Viruses are reprogrammed into vectors for cancer treatment based on three types of modification: targeting, arming and shielding. Viruses that are turned into therapeutics are beginning to find their place in cancer clinical practice, in combination with chemotherapy and radiation.The principles of virus reprogramming are illustrated in this article using adenovirus, a DNA virus with a naked icosahedral capsid, and measles virus, an enveloped RNA virus with a helical capsid. Targeting introduces multiple layers of cancer specificity, thereby improving safety and efficacy. The four basic layers of specificity are: particle activation through cancer-specific proteases; cell entry through cancer-specific cell-surface proteins; control of viral transcription and replication by tissue-specific promoters; and preferential spread of viruses that exploit cancer-specific molecular defects. Arming occurs through genes that express prodrug convertases, pro-apoptotic proteins or immuno-activating proteins. Coating with polymers and sequential usage of different envelopes or capsids provides shielding from the host immune response.The window of therapeutic opportunity can be extended by temporary immunosuppression. A five-step plan to turn a virus of choice into a potential oncolytic is discussed.

*Chuong, E. B. (2018). The placenta goes viral: Retroviruses control gene expression in pregnancy.PLoS Biology, 16(10), e3000028. [PDF] [Cited by]

The co-option of endogenous retroviruses (ERVs) is increasingly recognized as a recurrent theme in placental biology, which has far-reaching implications for our understanding of mammalian evolution and reproductive health. Most research in this area has focused on ERV-derived proteins, which have been repeatedly co-opted to promote cell-cell fusion and immune modulation in the placenta. ERVs also harbor regulatory sequences that can potentially control placental gene expression, but there has been limited evidence to support this role. In a recent study, Dunn-Fletcher and colleagues discover a striking example of an ERV-derived enhancer element that has been co-opted to regulate a gene important for human pregnancy. Using genomic and experimental approaches, they firmly establish that a primate-specific ERV functions as a placenta-specific enhancer for corticotropin-releasing hormone (CRH), a hormone linked to the control of birth timing in humans. Their findings implicate an extensive yet understudied role for retroviruses in shaping the evolution of placental gene regulatory networks.”

*Forterre, P. (2006). The origin of viruses and their possible roles in major evolutionary transitions. Virus Research, 117(1), 5-16. [Cited by]

“Viruses infecting cells from the three domains of life, Archaea, Bacteria and Eukarya, share homologous features, suggesting that viruses originated very early in the evolution of life. The three current hypotheses for virus origin, e.g. the virus first, the escape and the reduction hypotheses are revisited in this new framework. Theoretical considerations suggest that RNA viruses may have originated in the nucleoprotein world by escape or reduction from RNA-cells, whereas DNA viruses (at least some of them) might have evolved directly from RNA viruses. The antiquity of viruses can explain why most viral proteins have no cellular homologues or only distantly related ones. Viral proteins have replaced the ancestral bacterial RNA/DNA polymerases and primase during mitochondrial evolution. It has been suggested that replacement of cellular proteins by viral ones also occurred in early evolution of the DNA replication apparatus and/or that some DNA replication proteins originated directly in the virosphere and were later on transferred to cellular organisms. According to these new hypotheses, viruses played a critical role in major evolutionary transitions, such as the invention of DNA and DNA replication mechanisms, the formation of the three domains of life, or else, the origin of the eukaryotic nucleus.”

*Miest, T. S., & Cattaneo, R. (2014). New viruses for cancer therapy: Meeting clinical needs. Nature Reviews.Microbiology, 12(1), 23-34. [PDF] [Cited by]

Oncolytic virotherapy re-engineers and repurposes replicating viruses for the treatment of cancer. Therapeutic viruses specifically infect and spread within cancer tissue, causing cell death. In recent years, an increasing number of viruses have been developed as cancer therapeutics. There are nine virus families that are currently used in virotherapy clinical trials. Different viruses have evolved tissue specificities that can be exploited to preferentially destroy certain tumor types. Engineering strategies to improve the therapeutic potential of oncolytic viruses include protection from neutralizing immunity, restriction of entry or replication to tumor cells and expression of transgenes to synergize with traditional therapies and the anti-tumor activity of the patient’s immune system. Ion transport transgenes, such as the sodium-iodide symporter (NIS), can be used to image virus replication non-invasively at high resolutions using clinically available imaging technologies, such as single-photon emission computed tomography-computed tomography (SPECT-CT) and positron emission tomography (PET). The individualization of therapy and our increasing knowledge of tumor pathophysiology will guide the application of engineered viruses against tumor types that have defined sensitivities to virotherapy.”

*Roossinck, M. J. (2011). The good viruses: Viral mutualistic symbioses. Nature Reviews. Microbiology, 9(2), 99-108. [PDF] [Cited by]

Viruses have traditionally been thought of as pathogens, but many confer a benefit to their hosts and some are essential for the host life cycle. The polydnaviruses of endoparasitoid wasps have evolved with their hosts to become essential. Many of the viral genes are now encoded in the host nucleus. Endogenous retroviruses are abundant in many genomes of higher eukaryotes, and some have been involved in the evolution of their hosts, such as placental mammals. Some mammalian viruses can protect their hosts from infection by related viruses or from disease caused by completely unrelated pathogens, such as bubonic plague. Viruses can protect their hosts by killing off competitors, as is seen with the killer viruses in yeasts. A fungal virus confers thermal tolerance to a plant in a complex symbiosis involving its fungal host and the plant that the fungus colonizes. Several acute plant viruses confer conditional mutualism by enhancing drought tolerance in plants. Insect viruses have numerous mutualistic relationships with their hosts; in addition, viruses play parts in bacterium-insect mutualisms.”

*Roossinck, M. J. (2019). Viruses in the phytobiome. Current Opinion in Virology, 37, 72-76. [Cited by]

The phytobiome, defined as plants and all the entities that interact with them, is rich in viruses, but with the exception of plant viruses of crop plants, most of the phytobiome viruses remain very understudied. This review focuses on the neglected portions of the phytobiome, including viruses of other microbes interacting with plants, viruses in the soil, viruses of wild plants, and relationships between viruses and the vectors of plant viruses.

*Xu, P., Chen, F., Mannas, J. P., Feldman, T., Sumner, L. W., & Roossinck, M. J. (2008). Virus infection improves drought tolerance. The New Phytologist, 180(4), 911-921. [PDF] [Cited by]

“Viruses are obligate intracellular symbionts. Plant viruses are often discovered and studied as pathogenic parasites that cause diseases in agricultural plants. However, here it is shown that viruses can extend survival of their hosts under conditions of abiotic stress that could benefit hosts if they subsequently recover and reproduce. Various plant species were inoculated with four different RNA viruses, Brome mosaic virus (BMV), Cucumber mosaic virus (CMV), Tobacco mosaic virus and Tobacco rattle virus. The inoculated plants were stressed by withholding water. The onset of drought symptoms in virus-infected plants was compared with that in the plants that were inoculated with buffer (mock-inoculated plants). Metabolite profiling analysis was conducted and compared between mock-inoculated and virus-infected plants before and after being subjected to drought stress. In all cases, virus infection delayed the appearance of drought symptoms. Beet plants infected with CMV also exhibited significantly improved tolerance to freezing. Metabolite profiling analysis showed an increase in several osmoprotectants and antioxidants in BMV-infected rice and CMV-infected beet plants before and after drought stress. These results indicate that virus infection improves plant tolerance to abiotic stress, which correlates with increased osmoprotectant and antioxidant levels in infected plants.”

Questions? Please let me know (engelk@grinnell.edu).

 

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