Ross River Virus Immune Evasion Strategies and the Relevance to Post-viral Fatigue, and Myalgic Encephalomyelitis Onset

Frontiers in Medicine ◽

10.3389/fmed.2021.662513 ◽

2021 ◽

Vol 8 ◽

Author(s):

Brett A. Lidbury

Keyword(s):

Immune Evasion ◽

Chikungunya Virus ◽

Inflammatory Responses ◽

Myalgic Encephalomyelitis ◽

Ross River Virus ◽

Gene Suppression ◽

A Genome ◽

Cellular Immune ◽

Energy Pathways

Ross River virus (RRV) is an endemic Australian arbovirus, and member of the Alphavirus family that also includes Chikungunya virus (CHIK). RRV is responsible for the highest prevalence of human disease cases associated with mosquito-borne transmission in Australia, and has long been a leading suspect in cases of post-viral fatigue syndromes, with extrapolation of this link to Myalgic Encephalomyelitis (ME). Research into RRV pathogenesis has revealed a number of immune evasion strategies, impressive for a virus with a genome size of 12 kb (plus strand RNA), which resonate with insights into viral pathogenesis broadly. Drawing from observations on RRV immune evasion, mechanisms of relevance to long term idiopathic fatigue are featured as a perspective on infection and eventual ME symptoms, which include considerations of; (1) selective pro-inflammatory gene suppression post antibody-dependent enhancement (ADE) of RRV infection, (2) Evidence from other virus families of immune disruption and evasion post-ADE, and (3) how virally-driven immune evasion may impact on mitochondrial function via target of rapamycin (TOR) complexes. In light of these RRV measures to counter the host immune - inflammatory responses, links to recent discoveries explaining cellular, immune and metabolomic markers of ME will be explored and discussed, with the implications for long-COVID post SARS-CoV-2 also considered. Compelling issues on the connections between virally-induced alterations in cytokine expression, for example, will be of particular interest in light of energy pathways, and how these perturbations manifest clinically.

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Comparable Long-Term Rabies Immunity in Foxes after IntraMuscular and Oral Application Using a Third-Generation Oral Rabies Virus Vaccine

Vaccines ◽

10.3390/vaccines9010049 ◽

2021 ◽

Vol 9 (1) ◽

pp. 49

Author(s):

Verena te Kamp ◽

Virginia Friedrichs ◽

Conrad M. Freuling ◽

Ad Vos ◽

Madlin Potratz ◽

...

Keyword(s):

Immune Response ◽

Rabies Virus ◽

Specific Binding ◽

Lethal Dose ◽

Genetically Engineered ◽

Routes Of Administration ◽

Safety Studies ◽

Oral Rabies Vaccine ◽

Cellular Immune

The live genetically-engineered oral rabies virus (RABV) variant SPBN GASGAS induces long-lasting immunity in foxes and protection against challenge with an otherwise lethal dose of RABV field strains both after experimental oral and parenteral routes of administration. Induction of RABV-specific binding antibodies and immunoglobulin isotypes (IgM, total IgG, IgG1, IgG2) were comparable in orally and parenterally vaccinated foxes. Differences were only observed in the induction of virus-neutralizing (VNA) titers, which were significantly higher in the parenterally vaccinated group. The dynamics of rabies-specific antibodies pre- and post-challenge (365 days post vaccination) suggest the predominance of type-1 immunity protection of SPBN GASGAS. Independent of the route of administration, in the absence of IgG1 the immune response to SPBN GAGAS was mainly IgG2 driven. Interestingly, vaccination with SPBN GASGAS does not cause significant differences in inducible IFN-γ production in vaccinated animals, indicating a relatively weak cellular immune response during challenge. Notably, the parenteral application of SPBN GASGAS did not induce any adverse side effects in foxes, thus supporting safety studies of this oral rabies vaccine in various species.

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Impact of a long-term high-glucose environment on pro-inflammatory responses in macrophages stimulated with lipopolysaccharide

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/s00210-021-02137-8 ◽

2021 ◽

Vol 394 (10) ◽

pp. 2129-2139

Author(s):

Tokiko Suzuki ◽

Shigeyuki Yamashita ◽

Kohshi Hattori ◽

Naoyuki Matsuda ◽

Yuichi Hattori

Keyword(s):

High Glucose ◽

Inflammatory Responses

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Long-term sequelae of chikungunya virus disease: A systematic review

Travel Medicine and Infectious Disease ◽

10.1016/j.tmaid.2017.01.004 ◽

2017 ◽

Vol 15 ◽

pp. 8-22 ◽

Cited By ~ 64

Author(s):

Mariëlle van Aalst ◽

Charlotte Marieke Nelen ◽

Abraham Goorhuis ◽

Cornelis Stijnis ◽

Martin Peter Grobusch

Keyword(s):

Systematic Review ◽

Chikungunya Virus ◽

Virus Disease

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Leishmania donovani infection suppresses Allograft Inflammatory Factor-1 in monocytes and macrophages to inhibit inflammatory responses

Scientific Reports ◽

10.1038/s41598-020-79068-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ricardo Louzada da Silva ◽

Diana M. Elizondo ◽

Nailah Z. D. Brandy ◽

Naomi L. Haddock ◽

Thomas A. Boddie ◽

...

Keyword(s):

Immune Evasion ◽

Inflammatory Cytokine ◽

Leishmania Donovani ◽

Cytokine Production ◽

Inflammatory Responses ◽

Bone Marrow Cells ◽

Parasitic Infections ◽

Inflammatory Factor ◽

Immune Functions ◽

Inflammatory Cytokine Production

AbstractMacrophages and monocytes are important for clearance of Leishmania infections. However, immune evasion tactics employed by the parasite results in suppressed inflammatory responses, marked by deficient macrophage functions and increased accumulation of monocytes. This results in an ineffective ability to clear parasite loads. Allograft Inflammatory Factor-1 (AIF1) is expressed in myeloid cells and serves to promote immune responses. However, AIF1 involvement in monocyte and macrophage functions during parasitic infections has not been explored. This study now shows that Leishmania donovani inhibits AIF1 expression in macrophages to block pro-inflammatory responses. Mice challenged with the parasite had markedly reduced AIF1 expression in splenic macrophages. Follow-up studies using in vitro approaches confirmed that L. donovani infection in macrophages suppresses AIF1 expression, which correlated with reduction in pro-inflammatory cytokine production and increased parasite load. Ectopic overexpression of AIF1 in macrophages provided protection from infection, marked by robust pro-inflammatory cytokine production and efficient pathogen clearance. Further investigations found that inhibiting AIF1 expression in bone marrow cells or monocytes impaired differentiation into functional macrophages. Collectively, results show that AIF1 is a critical regulatory component governing monocyte and macrophage immune functions and that L. donovani infection can suppress the gene as an immune evasion tactic.

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Long-Term Glucose Starvation Induces Inflammatory Responses and Phenotype Switch in Primary Cortical Rat Astrocytes

Journal of Molecular Neuroscience ◽

10.1007/s12031-021-01800-2 ◽

2021 ◽

Author(s):

Vanessa Kogel ◽

Stefanie Trinh ◽

Natalie Gasterich ◽

Cordian Beyer ◽

Jochen Seitz

Keyword(s):

Cerebral Cortex ◽

Synapse Formation ◽

Inflammatory Responses ◽

Glucose Starvation ◽

Unfolded Protein ◽

Genes Encoding ◽

Phenotype Switch ◽

The Unfolded Protein Response ◽

The Brain

AbstractAstrocytes are the most abundant cell type in the brain and crucial to ensure the metabolic supply of neurons and their synapse formation. Overnutrition as present in patients suffering from obesity causes astrogliosis in the hypothalamus. Other diseases accompanied by malnutrition appear to have an impact on the brain and astrocyte function. In the eating disorder anorexia nervosa (AN), patients suffer from undernutrition and develop volume reductions of the cerebral cortex, associated with reduced astrocyte proliferation and cell count. Although an effect on astrocytes and their function has already been shown for overnutrition, their role in long-term undernutrition remains unclear. The present study used primary rat cerebral cortex astrocytes to investigate their response to chronic glucose starvation. Cells were grown with a medium containing a reduced glucose concentration (2 mM) for 15 days. Long-term glucose starvation increased the expression of a subset of pro-inflammatory genes and shifted the primary astrocyte population to the pro-inflammatory A1-like phenotype. Moreover, genes encoding for proteins involved in the unfolded protein response were elevated. Our findings demonstrate that astrocytes under chronic glucose starvation respond with an inflammatory reaction. With respect to the multiple functions of astrocytes, an association between elevated inflammatory responses due to chronic starvation and alterations found in the brain of patients suffering from undernutrition seems possible.

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Genome Sequence Analysis of First Ross River Virus Isolate from Papua New Guinea Indicates Long-Term, Local Evolution

Viruses ◽

10.3390/v13030482 ◽

2021 ◽

Vol 13 (3) ◽

pp. 482

Author(s):

Alice Michie ◽

John S. Mackenzie ◽

David W. Smith ◽

Allison Imrie

Keyword(s):

Papua New Guinea ◽

Large Scale ◽

Solomon Islands ◽

Febrile Illness ◽

New Guinea ◽

Recent Common Ancestor ◽

Ross River Virus ◽

Most Recent Common Ancestor ◽

Mean Time

Ross River virus (RRV) is the most medically significant mosquito-borne virus of Australia, in terms of human morbidity. RRV cases, characterised by febrile illness and potentially persistent arthralgia, have been reported from all Australian states and territories. RRV was the cause of a large-scale epidemic of multiple Pacific Island countries and territories (PICTs) from 1979 to 1980, involving at least 50,000 cases. Historical evidence of RRV seropositivity beyond Australia, in populations of Papua New Guinea (PNG), Indonesia and the Solomon Islands, has been documented. We describe the genomic characterisation and timescale analysis of the first isolate of RRV to be sampled from PNG to date. Our analysis indicates that RRV has evolved locally within PNG, independent of Australian lineages, over an approximate 40 year period. The mean time to most recent common ancestor (tMRCA) of the unique PNG clade coincides with the initiation of the PICTs epidemic in mid-1979. This may indicate that an ancestral variant of the PNG clade was seeded into the region during the epidemic, a period of high RRV transmission. Further epidemiological and molecular-based surveillance is required in PNG to better understand the molecular epidemiology of RRV in the general Australasian region.

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Chikungunya Virus-associated Long-term Arthralgia: A 36-month Prospective Longitudinal Study

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0002137 ◽

2013 ◽

Vol 7 (3) ◽

pp. e2137 ◽

Cited By ~ 210

Author(s):

Clémentine Schilte ◽

Frédérik Staikovsky ◽

Thérèse Couderc ◽

Yoann Madec ◽

Florence Carpentier ◽

...

Keyword(s):

Longitudinal Study ◽

Chikungunya Virus ◽

Prospective Longitudinal Study ◽

Prospective Longitudinal

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Accumulation of mutations in sexual and asexual populations

Genetics Research ◽

10.1017/s0016672300026938 ◽

1987 ◽

Vol 49 (2) ◽

pp. 135-146 ◽

Cited By ~ 98

Author(s):

Pekka Pamilo ◽

Masatoshi Nei ◽

Wen-Hsiung Li

Keyword(s):

Weak Selection ◽

Population Variance ◽

Asexual Population ◽

Term Evolution ◽

A Genome ◽

Analytical Formulae ◽

The Mean ◽

Asexual Populations ◽

Mutant Genes

SummaryThe accumulation of beneficial and harmful mutations in a genome is studied by using analytical methods as well as computer simulation for different modes of reproduction. The modes of reproduction examined are biparental (bisexual, hermaphroditic), uniparental (selfing, automictic, asexual) and mixed (partial selfing, mixture of hermaphroditism and parthenogenesis). It is shown that the rates of accumulation of both beneficial and harmful mutations with weak selection depend on the within-population variance of the number of mutant genes per genome. Analytical formulae for this variance are derived for neutral mutant genes for hermaphroditic, selfing and asexual populations; the neutral variance is largest in a selfing population and smallest in an asexual population. Directional selection reduces the population variance in most cases, whereas recombination partially restores the reduced variance. Therefore, biparental organisms accumulate beneficial mutations at the highest rate and harmful mutations at the lowest rate. Selfing organisms are intermediate between biparental and asexual organisms. Even a limited amount of outcrossing in largely selfing and parthenogenetic organisms markedly affects the accumulation rates. The accumulation of mutations is likely to affect the mean population fitness only in long-term evolution.

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