Host Synthesized Carbohydrate Antigens on Viral Glycoproteins as “Achilles’ Heel” of Viruses Contributing to Anti-Viral Immune Protection

The glycans on enveloped viruses are synthesized by host-cell machinery. Some of these glycans on zoonotic viruses of mammalian reservoirs are recognized by human natural antibodies that may protect against such viruses. These antibodies are produced mostly against carbohydrate antigens on gastrointestinal bacteria and fortuitously, they bind to carbohydrate antigens synthesized in other mammals, neutralize and destroy viruses presenting these antigens. Two such antibodies are: anti-Gal binding to α-gal epitopes synthesized in non-primate mammals, lemurs, and New World monkeys, and anti-N-glycolyl neuraminic acid (anti-Neu5Gc) binding to N-glycolyl-neuraminic acid (Neu5Gc) synthesized in apes, Old World monkeys, and many non-primate mammals. Anti-Gal appeared in Old World primates following accidental inactivation of the α1,3galactosyltransferase gene 20–30 million years ago. Anti-Neu5Gc appeared in hominins following the inactivation of the cytidine-monophosphate-N-acetyl-neuraminic acid hydroxylase gene, which led to the loss of Neu5Gc <6 million-years-ago. It is suggested that an epidemic of a lethal virus eliminated ancestral Old World-primates synthesizing α-gal epitopes, whereas few mutated offspring lacking α-gal epitopes and producing anti-Gal survived because anti-Gal destroyed viruses presenting α-gal epitopes, following replication in parental populations. Similarly, anti-Neu5Gc protected few mutated hominins lacking Neu5Gc in lethal virus epidemics that eliminated parental hominins synthesizing Neu5Gc. Since α-gal epitopes are presented on many zoonotic viruses it is suggested that vaccines elevating anti-Gal titers may be of protective significance in areas endemic for such zoonotic viruses. This protection would be during the non-primate mammal to human virus transmission, but not in subsequent human to human transmission where the virus presents human glycans. In addition, production of viral vaccines presenting multiple α-gal epitopes increases their immunogenicity because of effective anti-Gal-mediated targeting of vaccines to antigen presenting cells for extensive uptake of the vaccine by these cells.

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Human Natural Antibodies to Mammalian Carbohydrate Antigens as Unsung Heroes Protecting against Past, Present, and Future Viral Infections

Antibodies ◽

10.3390/antib9020025 ◽

2020 ◽

Vol 9 (2) ◽

pp. 25 ◽

Cited By ~ 6

Author(s):

Uri Galili

Keyword(s):

Blood Group ◽

Viral Infections ◽

Mammalian Species ◽

Natural Antibodies ◽

New World Monkeys ◽

Old World Monkeys ◽

Carbohydrate Antigens ◽

Old World ◽

Enveloped Virus ◽

Zoonotic Viruses

Human natural antibodies to mammalian carbohydrate antigens (MCA) bind to carbohydrate-antigens synthesized in other mammalian species and protect against zoonotic virus infections. Three such anti-MCA antibodies are: (1) anti-Gal, also produced in Old-World monkeys and apes, binds to α-gal epitopes synthesized in non-primate mammals, lemurs, and New-World monkeys; (2) anti-Neu5Gc binds to Neu5Gc (N-glycolyl-neuraminic acid) synthesized in apes, Old-World monkeys, and many non-primate mammals; and (3) anti-Forssman binds to Forssman-antigen synthesized in various mammals. Anti-viral protection by anti-MCA antibodies is feasible because carbohydrate chains of virus envelopes are synthesized by host glycosylation machinery and thus are similar to those of their mammalian hosts. Analysis of MCA glycosyltransferase genes suggests that anti-Gal appeared in ancestral Old-World primates following catastrophic selection processes in which parental populations synthesizing α-gal epitopes were eliminated in enveloped virus epidemics. However, few mutated offspring in which the α1,3galactosyltransferase gene was accidentally inactivated produced natural anti-Gal that destroyed viruses presenting α-gal epitopes, thereby preventing extinction of mutated offspring. Similarly, few mutated hominin offspring that ceased to synthesize Neu5Gc produced anti-Neu5Gc, which destroyed viruses presenting Neu5Gc synthesized in parental hominin populations. A present-day example for few humans having mutations that prevent synthesis of a common carbohydrate antigen (produced in >99.99% of humans) is blood-group Bombay individuals with mutations inactivating H-transferase; thus, they cannot synthesize blood-group O (H-antigen) but produce anti-H antibody. Anti-MCA antibodies prevented past extinctions mediated by enveloped virus epidemics, presently protect against zoonotic-viruses, and may protect in future epidemics. Travelers to regions with endemic zoonotic viruses may benefit from vaccinations elevating protective anti-MCA antibody titers.

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Biosynthesis of α-Gal Epitopes (Galα1-3Galβ1-4GlcNAc-R) and Their Unique Potential in Future α-Gal Therapies

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.746883 ◽

2021 ◽

Vol 8 ◽

Author(s):

Uri Galili

Keyword(s):

Carbohydrate Antigen ◽

Healing Time ◽

New World Monkeys ◽

Old World Monkeys ◽

Old World ◽

Enveloped Virus ◽

Zoonotic Viruses ◽

Chemotactic Peptides ◽

Antigen Presenting

The α-gal epitope is a carbohydrate antigen which appeared early in mammalian evolution and is synthesized in large amounts by the glycosylation enzyme α1,3galactosyltransferase (α1,3GT) in non-primate mammals, lemurs, and New-World monkeys. Ancestral Old-World monkeys and apes synthesizing α-gal epitopes underwent complete extinction 20–30 million years ago, and their mutated progeny lacking α-gal epitopes survived. Humans, apes, and Old-World monkeys which evolved from the surviving progeny lack α-gal epitopes and produce the natural anti-Gal antibody which binds specifically to α-gal epitopes. Because of this reciprocal distribution of the α-gal epitope and anti-Gal in mammals, transplantation of organs from non-primate mammals (e.g., pig xenografts) into Old-World monkeys or humans results in hyperacute rejection following anti-Gal binding to α-gal epitopes on xenograft cells. The in vivo immunocomplexing between anti-Gal and α-gal epitopes on molecules, pathogens, cells, or nanoparticles may be harnessed for development of novel immunotherapies (referred to as “α-gal therapies”) in various clinical settings because such immune complexes induce several beneficial immune processes. These immune processes include localized activation of the complement system which can destroy pathogens and generate chemotactic peptides that recruit antigen-presenting cells (APCs) such as macrophages and dendritic cells, targeting of antigens presenting α-gal epitopes for extensive uptake by APCs, and activation of recruited macrophages into pro-reparative macrophages. Some of the suggested α-gal therapies associated with these immune processes are as follows: 1. Increasing efficacy of enveloped-virus vaccines by synthesizing α-gal epitopes on vaccinating inactivated viruses, thereby targeting them for extensive uptake by APCs. 2. Conversion of autologous tumors into antitumor vaccines by expression of α-gal epitopes on tumor cell membranes. 3. Accelerating healing of external and internal injuries by α-gal nanoparticles which decrease the healing time and diminish scar formation. 4. Increasing anti-Gal–mediated protection against zoonotic viruses presenting α-gal epitopes and against protozoa, such as Trypanosoma, Leishmania, and Plasmodium, by vaccination for elevating production of the anti-Gal antibody. The efficacy and safety of these therapies were demonstrated in transgenic mice and pigs lacking α-gal epitopes and producing anti-Gal, raising the possibility that these α-gal therapies may be considered for further evaluation in clinical trials.

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491. Aerosol-Generating Medical Procedures: Transmission of SARS-CoV-2 and Emerging Viruses

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.684 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S312-S312

Author(s):

Seth D Judson ◽

Vincent J Munster

Keyword(s):

High Risk ◽

Severe Disease ◽

Experimental Studies ◽

Virus Transmission ◽

Nosocomial Transmission ◽

Medical Procedures ◽

Emerging Viruses ◽

Zoonotic Viruses ◽

Increased Risk ◽

Hospital Acquired

Abstract Background During the pandemic of coronavirus disease 2019 (COVID-19), many questions arose regarding risks for hospital-acquired or nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Aerosol generating medical procedures (AGMPs), techniques that can generate infectious, virus-laden aerosols, could potentially amplify transmission among healthcare workers (HCWs). Thus, it was widely recommended that HCWs use airborne precautions when performing AGMPs. However, in clinical settings it is often unclear what procedures constitute AGMPs and how the risk varies by procedure or pathogen. We set out to further define AGMPs and assess the risk for nosocomial transmission of SARS-CoV-2 and other high-risk viruses via AGMPs. Methods We identified potential AGMPs and emerging viruses that were high-risk for nosocomial transmission through reviewing experimental and clinical data. Potential AGMPs were those associated with previous virus transmission or mechanically capable of transmission. High-risk viruses were defined as those that cause severe disease in humans for which limited therapies or interventions exist, are infectious via aerosols in humans or non-human primates (NHPs), found in the respiratory tract of infected humans or NHPs, and had previous evidence of nosocomial transmission. Results We identified multiple potential AGMPs, which could be divided into those that generate aerosols or induce a patient to form aerosols, as well as eight families of high-risk viruses. All of the viruses were emerging zoonotic RNA viruses. In the family Coronaviridae, we identified potential evidence for SARS-CoV-1, MERS-CoV, and SARS-CoV-2 transmission via AGMPs. SARS-CoV-1 and SARS-CoV-2 were also found to be similarly stable when aerosolized. Conclusion Multiple emerging zoonotic viruses pose a high risk for nosocomial transmission through a variety of AGMPs. Given the similar stability of SARS-CoV-2 with SARS-CoV-1 when aerosolized and prior nosocomial transmission of SARS-CoV-1 via AGMPs, we suspect that certain AGMPs pose an increased risk for SARS-CoV-2 transmission. Additional experimental studies and on-site clinical sampling during AGMPs are necessary to further risk stratify AGMPs. Disclosures All Authors: No reported disclosures

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“Tho' she kneel'd in that place where they grew…” The uses and origins of primate colour vision

Journal of Experimental Biology ◽

10.1242/jeb.146.1.21 ◽

1989 ◽

Vol 146 (1) ◽

pp. 21-38 ◽

Cited By ~ 3

Author(s):

J. D. Mollon

Keyword(s):

X Chromosome ◽

Colour Vision ◽

Visual Pathway ◽

New World Monkeys ◽

Old World Monkeys ◽

Old World ◽

Early Stages ◽

Local Sign ◽

Retinal Photoreceptor ◽

Recent Duplication

The disabilities experienced by colour-blind people show us the biological advantages of colour vision in detecting targets, in segregating the visual field and in identifying particular objects or states. Human dichromats have especial difficulty in detecting coloured fruit against dappled foliage that varies randomly in luminosity; it is suggested that yellow and orange tropical fruits have co-evolved with the trichromatic colour vision of Old World monkeys. It is argued that the colour vision of man and of the Old World monkeys depends on two subsystems that remain parallel and independent at early stages of the visual pathway. The primordial subsystem, which is shared with most mammals, depends on a comparison of the rates of quantum catch in the short- and middle-wave cones; this system exists almost exclusively for colour vision, although the chromatic signals carry with them a local sign that allows them to sustain several of the functions of spatiochromatic vision. The second subsystem arose from the phylogenetically recent duplication of a gene on the X-chromosome, and depends on a comparison of the rates of quantum catch in the long- and middle-wave receptors. At the early stages of the visual pathway, this chromatic information is carried by a channel that is also sensitive to spatial contrast. The New World monkeys have taken a different route to trichromacy: in species that are basically dichromatic, heterozygous females gain trichromacy as a result of X-chromosome inactivation, which ensures that different photopigments are expressed in two subsets of retinal photoreceptor.

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Referential alarm calling behaviour in New World primates

Current Zoology ◽

10.1093/czoolo/58.5.680 ◽

2012 ◽

Vol 58 (5) ◽

pp. 680-697 ◽

Cited By ~ 13

Author(s):

Cristiane Cäsar ◽

Klaus Zuberbühler

Keyword(s):

New World ◽

General Pattern ◽

Referential Communication ◽

New World Monkeys ◽

Human Language ◽

New World Primates ◽

Ample Evidence ◽

Old World ◽

Call Type ◽

Wide Range

Abstract There is relatively good evidence that non-human primates can communicate about objects and events in their environment in ways that allow recipients to draw inferences about the nature of the event experienced by the signaller. In some species, there is also evidence that the basic semantic units are not individual calls, but call sequences and the combinations generated by them. These two findings are relevant to theories pertaining to the origins of human language because of the resemblances of these phenomena with linguistic reference and syntactic organisation. Until recently, however, most research efforts on the primate origins of human language have involved Old World species with comparatively few systematic studies on New World monkeys, which has prevented insights into the deeper phylogenetic roots and evolutionary origins of language-relevant capacities. To address this, we review the older primate literature and very recent evidence for functionally referential communication and call combinations in New World primates. Within the existing literature there is ample evidence in both Callitrichids and Ce-bids for acoustically distinct call variants given to external disturbances that are accompanied by distinct behavioural responses. A general pattern is that one call type is typically produced in response to a wide range of general disturbances, often on the ground but also including inter-group encounters, while another call type is produced in response to a much narrower range of aerial threats. This pattern is already described for Old World monkeys and Prosimians, suggesting an early evolutionary origin. Second, recent work with black-fronted titi monkeys has produced evidence for different alarm call sequences consisting of acoustically distinct call types. These sequences appear to encode several aspects of the predation event simultaneously, notably predator type and location. Since meaningful call sequences have already been described in Old World primates, we suggest that basic combinatorial vocal communication has evolved in the primate lineage long before the advent of language. Moreover, it is possible that some of these communicative abilities have evolved even earlier, or independently, as there is comparable evidence in other taxonomic groups. We discuss these findings in an attempt to shed further light on the primate stock from which human language has arisen.

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Pulmonary granuloma is not always the tuberculosis hallmark: pathological findings of different tuberculosis stages in New and Old World Nonhuman Primates naturally infected with the Mycobacterium tuberculosis Complex

10.21203/rs.3.rs-902471/v1 ◽

2021 ◽

Author(s):

Asheley H. B. Pereira ◽

Claudia A. A. Lopes ◽

Thalita A. Pissinatti ◽

Ana C. A. Pinto ◽

Daniel R. A. Oliveira ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

New World ◽

Nonhuman Primates ◽

World Monkey ◽

Histological Evaluation ◽

New World Monkeys ◽

Old World Monkeys ◽

Pathological Findings ◽

Old World ◽

Pulmonary Granuloma

Abstract Herein we present the pathological findings of different tuberculosis stages in Old and New World monkeys kept under human care in Rio de Janeiro, Brazil and naturally infected with Mycobacterium tuberculosis Complex. Fifteen nonhuman primates from five different colonies were incorporated into the study. There are 60% (9/15) Old World Monkeys and 40% (6/15) New World Monkeys. According to the gross and histopathologic findings, the lesions in nonhuman primates of this study are classified into the chronic-active, extrapulmonary, early-activation or latent-reactivation tuberculosis stage. Among the Old World Monkey, 66.7% (6/9) of nonhuman primates, all rhesus monkeys (Macaca mulatta), showed severe granulomatous pneumonia. In all Old World Monkeys cases, typical granulomas were seen in at least one organ regardless of the stage of the disease. In the New World Monkeys, the typical pulmonary granulomas were seen in 16.7% (1/6) of the cases, just in the latent-reactivation stage in Uta Hick’s Bearded Saki (Chiropotes utahickae). In this study, 66.7% (6/9) of Old World Monkeys (OWM) and 83.3% (5/6) of New World Monkeys (NWM) showed pulmonary changes at the histological evaluation. The tuberculosis diagnosis in the nonhuman primates in this study was based on pathological, immunohistochemical, molecular, and bacteriological culture. Although the typical presentation was observed in some cases, the absence of pulmonary granuloma did not exclude the tuberculosis occurrence in nonhuman primates of the Old and New World. Tuberculosis should be included as a cause of interstitial pneumonia with foamy macrophages infiltration in the New World nonhuman primates. Due to the high sensitivity of immunohistochemistry with Anti-Mycobacterium tuberculosis, we suggest the addition of this technique as a diagnostic tool of tuberculosis in the nonhuman primates even when the typical changes are not seen.

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Estimation and optimal control of the multi-scale dynamics of the Covid-19

10.1101/2021.03.04.21252880 ◽

2021 ◽

Author(s):

David Jaurès Fotsa-Mbogne ◽

Stéphane Yanick Tchoumi ◽

Yannick Kouakep-Tchaptchie ◽

Vivient Corneille Kamla ◽

Jean-Claude Kamgang ◽

...

Keyword(s):

Optimal Control ◽

Human Population ◽

Virus Transmission ◽

Scale Model ◽

Model Parameters ◽

Optimal Control Strategy ◽

Or Efficiency ◽

Human Virus ◽

Multi Scale ◽

Human Density

AbstractThis work aims at a better understanding and the optimal control of the spread of the new severe acute respiratory corona virus 2 (SARS-CoV-2). We first propose a multi-scale model giving insights on the virus population dynamics, the transmission process and the infection mechanism. We consider 10 compartments in the human population in order to take into accounts the effects of different specific mitigation policies: susceptible, infected, infectious, quarantined, hospitalized, treated, recovered, non-infectious dead, infectious dead, buried. The population of viruses is also partitioned into 10 compartments corresponding respectively to each of the first nine human population compartments and the free viruses available in the environment. Indeed, we have human to human virus transmission, human to environment virus transmission, environment to human virus transmission and self infection by susceptible individuals. We show the global stability of the disease free equilibrium if a given threshold 𝒯0 is less or equal to 1 and we provide how to compute the basic reproduction number ℛ0. A convergence index 𝒯1 is also defined in order to estimate the speed at which the disease extincts and an upper bound to the time of extinction is given. The existence of the endemic equilibrium is conditional and its description is provided. We evaluate the sensitivity of ℛ0, 𝒯0 and 𝒯1 to control parameters such as the maximal human density allowed per unit of surface, the rate of disinfection both for people and environment, the mobility probability, the wearing mask probability or efficiency, and the human to human contact rate which results from the previous one. Except the maximal human density allowed per unit of surface, all those parameters have significant effects on the qualitative dynamics of the disease. The most significant is the probability of wearing mask followed by the probability of mobility and the disinfection rate. According to a functional cost taking into consideration economic impacts of SARS-CoV-2, we determine and discuss optimal fighting strategies. The study is applied to real available data from Cameroon and an estimation of model parameters is done. After several simulations, social distancing and the disinfection frequency appear as the main elements of the optimal control strategy.

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HIV-1TransInfection of CD4+T Cells by Professional Antigen Presenting Cells

Scientifica ◽

10.1155/2013/164203 ◽

2013 ◽

Vol 2013 ◽

pp. 1-30 ◽

Cited By ~ 15

Author(s):

Charles R. Rinaldo

Keyword(s):

T Cells ◽

Virus Replication ◽

Virus Transmission ◽

Antigen Presenting Cells ◽

Activated T Cells ◽

Infection Processes ◽

The Many ◽

Antigen Presenting ◽

Hiv 1 ◽

Virus Subtype

Since the 1990s we have known of the fascinating ability of a complex set of professional antigen presenting cells (APCs; dendritic cells, monocytes/macrophages, and B lymphocytes) to mediate HIV-1transinfection of CD4+T cells. This results in a burst of virus replication in the T cells that is much greater than that resulting from direct,cisinfection of either APC or T cells, ortransinfection between T cells. Such APC-to-T celltransinfection first involves a complex set of virus subtype, attachment, entry, and replication patterns that have many similarities among APC, as well as distinct differences related to virus receptors, intracellular trafficking, and productive and nonproductive replication pathways. The end result is that HIV-1 can sequester within the APC for several days and be transmitted via membrane extensions intracellularly and extracellularly to T cells across the virologic synapse. Virus replication requires activated T cells that can develop concurrently with the events of virus transmission. Further research is essential to fill the many gaps in our understanding of thesetransinfection processes and their role in natural HIV-1 infection.

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The Major Histocompatibility Complex of Old World Camels—A Synopsis

Cells ◽

10.3390/cells8101200 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1200 ◽

Cited By ~ 1

Author(s):

Plasil ◽

Wijkmark ◽

Elbers ◽

Oppelt ◽

Burger ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class I ◽

Mhc Class Ii ◽

Class Ii ◽

Class I ◽

Class Iii ◽

Old World ◽

Histocompatibility Complex ◽

Mhc Class Iii ◽

Antigen Presenting

This study brings new information on major histocompatibility complex (MHC) class III sub-region genes in Old World camels and integrates current knowledge of the MHC region into a comprehensive overview for Old World camels. Out of the MHC class III genes characterized, TNFA and the LY6 gene family showed high levels of conservation, characteristic for MHC class III loci in general. For comparison, an MHC class II gene TAP1, not coding for antigen presenting molecules but functionally related to MHC antigen presenting functions was studied. TAP1 had many SNPs, even higher than the MHC class I and II genes encoding antigen presenting molecules. Based on this knowledge and using new camel genomic resources, we constructed an improved genomic map of the entire MHC region of Old World camels. The MHC class III sub-region shows a standard organization similar to that of pig or cattle. The overall genomic structure of the camel MHC is more similar to pig MHC than to cattle MHC. This conclusion is supported by differences in the organization of the MHC class II sub-region, absence of functional DY genes, different organization of MIC genes in the MHC class I sub-region, and generally closer evolutionary relationships of camel and porcine MHC gene sequences analyzed so far.

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Test of the Law of Initial Values in Four Species of Primates

Psychological Reports ◽

10.2466/pr0.1972.30.1.191 ◽

1972 ◽

Vol 30 (1) ◽

pp. 191-195 ◽

Cited By ~ 1

Author(s):

Thomas B. Downer ◽

William D. Thompson

Keyword(s):

Auditory Stimulus ◽

New World ◽

New World Monkeys ◽

World Species ◽

Old World ◽

Heart Rates ◽

Initial Values ◽

The Law

The law of initial values was tested in the serial responses of monkeys to an auditory stimulus. The “law” was not confirmed for heart rates. GSRs were absent in the new world monkeys but supported the law of initial values for half of the Ss of old world species. Less support was found when conductance scores were used.

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