Summary: Evolution of RNA viruses occurs through disequilibria of collections of closely related mutant spectra or mutant clouds termed viral quasispecies. Here we review the origin of the quasispecies concept and some biological implications of quasispecies dynamics. Two main aspects are addressed: (i) mutant clouds as reservoirs of phenotypic variants for virus adaptability and (ii) the internal interactions that are established within mutant spectra that render a virus ensemble the unit of selection. The understanding of viruses as quasispecies has led to new antiviral designs, such as lethal mutagenesis, whose aim is to drive viruses toward low fitness values with limited chances of fitness recovery. The impact of quasispecies for three salient human pathogens, human immunodeficiency virus and the hepatitis B and C viruses, is reviewed, with emphasis on antiviral treatment strategies. Finally, extensions of quasispecies to nonviral systems are briefly mentioned to emphasize the broad applicability of quasispecies theory.

Viral Quasispecies Evolution

Rodents are the most abundant and diversified order of living mammals in the world. Already since the Middle Ages we know that they can contribute to human disease, as black rats were associated with distribution of plague. However, also in modern times rodents form a threat for public health. In this review article a large number of pathogens that are directly or indirectly transmitted by rodents are described. Moreover, a simplified rodent disease model is discussed.

Rodent-borne diseases and their risks for public health

Passive serotherapy can confer immediate protection against microbial infection, but methods to rapidly generate human neutralizing monoclonal antibodies are not yet available. We have developed an improved method for Epstein-Barr virus transformation of human B cells. We used this method to analyze the memory repertoire of a patient who recovered from severe acute respiratory syndrome coronavirus (SARS-CoV) infection and to isolate monoclonal antibodies specific for different viral proteins, including 35 antibodies with in vitro neutralizing activity ranging from 10(-8)M to 10(-11)M. One such antibody confers protection in vivo in a mouse model of SARS-CoV infection. These results show that it is possible to interrogate the memory repertoire of immune donors to rapidly and efficiently isolate neutralizing antibodies that have been selected in the course of natural infection.

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An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus

Phlebotomine sandflies transmit pathogens that affect humans and animals worldwide. We review the roles of phlebotomines in the spreading of leishmaniases, sandfly fever, summer meningitis, vesicular stomatitis, Chandipura virus encephalitis and Carrion's disease. Among over 800 species of sandfly recorded, 98 are proven or suspected vectors of human leishmaniases; these include 42 Phlebotomus species in the Old World and 56 Lutzomyia species in the New World (all: Diptera: Psychodidae). Based on incrimination criteria, we provide an updated list of proven or suspected vector species by endemic country where data are available. Increases in sandfly diffusion and density resulting from increases in breeding sites and blood sources, and the interruption of vector control activities contribute to the spreading of leishmaniasis in the settings of human migration, deforestation, urbanization and conflict. In addition, climatic changes can be expected to affect the density and dispersion of sandflies. Phlebovirus infections and diseases are present in large areas of the Old World, especially in the Mediterranean subregion, in which virus diversity has proven to be higher than initially suspected. Vesiculovirus diseases are important to livestock and humans in the southeastern U.S.A. and Latin America, and represent emerging human threats in parts of India. Carrion's disease, formerly restricted to regions of elevated altitude in Peru, Ecuador and Colombia, has shown recent expansion to non-endemic areas of the Amazon basin.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-2915.2012.01034.x

Phlebotomine sandflies and the spreading of leishmaniases and other diseases of public health concern

Ebola virus causes hemorrhagic fever in humans and nonhuman primates, resulting in mortality rates of up to 90%. Studies of this virus have been hampered by its extraordinary pathogenicity, which requires biosafety level 4 containment. To circumvent this problem, we developed a novel complementation system for functional analysis of Ebola virus glycoproteins. It relies on a recombinant vesicular stomatitis virus (VSV) that contains the green fluorescent protein gene instead of the receptor-binding G protein gene (VSVΔG*). Herein we show that Ebola Reston virus glycoprotein (ResGP) is efficiently incorporated into VSV particles. This recombinant VSV with integrated ResGP (VSVΔG*-ResGP) infected primate cells more efficiently than any of the other mammalian or avian cells examined, in a manner consistent with the host range tropism of Ebola virus, whereas VSVΔG* complemented with VSV G protein (VSVΔG*-G) efficiently infected the majority of the cells tested. We also tested the utility of this system for investigating the cellular receptors for Ebola virus. Chemical modification of cells to alter their surface proteins markedly reduced their susceptibility to VSVΔG*-ResGP but not to VSVΔG*-G. These findings suggest that cell surface glycoproteins with N-linked oligosaccharide chains contribute to the entry of Ebola viruses, presumably acting as a specific receptor and/or cofactor for virus entry. Thus, our VSV system should be useful for investigating the functions of glycoproteins from highly pathogenic viruses or those incapable of being cultured in vitro.

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A system for functional analysis of Ebola virus glycoprotein

Glycosylation and oligomerization of the spike protein of marburg virus

Table of Contents 1. Viral Zoonoses Introduction Cycles of Arbovirus Infections Zoonoses Caused by Alphaviruses Zoonoses Caused by Flaviviruses Zoonoses Caused by Bunyaviruses Zoonoses Caused by Reoviruses (Coltiviridae and Orbivirdae) Zoonoses Caused by Arenaviruses Zoonoses Caused by Filoviruses Zoonoses Caused by Rhabdoviruses Zoonoses Caused by Paramyxoviruses Zoonoses Caused by Orthomyxoviruses Zoonoses Caused by Picornaviruses Zoonoses Caused by Herpesviruses Zoonoses Caused by Poxviruses Zoones Associated with Prions 2. Bacterial Zoonoses Introduction Anthrax Bartonelloses, Including Cat Scratch Disease Borrelioses Brucelloses Campylobacteriosis due to Campylobacter jejuni, C. coli, C. lari, and C. upsaliensis Capnocytophaga Infections Chlamydial Infections Ehrlichioses Enterohemorrhagic Escherichia coli Infections Erysipeloid Glanders (Malleus, or Farcy) Leptospiroses Listeriosis Melioidosis Mycobacterial Infections Pasteurelloses Plague Rat Bite Fever Rickettsioses Salmonelloses Staphylococcal Infections Streptococcal Infections Tularemia Vibrioses Yersinioses Caused by Yersinia enterocolitica and Yersinia pseudotuberculosis Bacteria That Have Rarely Been Incriminated as Agents of Zoonoses 3. Fungal Zoonoses Introduction Dermatophytoses Caused by Microsporum Species Dermatophytoses Caused by Trichophyton Species Sporotrichosis 4. Parasitic Zoonoses Introduction Zoonoses Caused by Protozoa Zoonoses Caused by Trematodes Zoonoses Caused by Cestodes Zoonoses Caused by Nematodes Zoonoses Caused by Acanthocephala Zoonoses Caused by Arthropods Pentastomidosis Appendix A: Animal Bite Infections Appendix B: Infections and Intoxications Transmissible by Foodstuffs of Animal Origin Appendix C: Iatrogenic Transmission of Zoonotic Agents Appendix D: Zoonotic Diseases Notifiable at the National Level, United States, 2002 Appendix E: Zoonoses Involving Various Types of Animals

Zoonoses: Infectious Diseases Transmissible from Animals to Humans

Release of Viral Glycoproteins during Ebola Virus Infection

Written by veterinarians, medical microbiologists, and physicians with broad experience in the field of infectious diseases, this valuable physician's reference covers all aspects of epidemiology, diagnosis, and differential diagnosis, as well as therapy and prophylaxis of zoonotic diseases.
Among the topics covered are zoonotic pathogens as agents of biological warfare, emergence and re-emergence of zoonotic diseases, opportunistic zoonotic infections, risks of xenotransplantation, imported zoonotic infections, food-borne zoonoses, and transmissible spongiform encephalopathies. It also examines the most advanced diagnostic techniques, include PCR and ELISA, for the detection of sporadic infections even with rare organisms.
Zoonoses is a valuable desk top reference for professionals in medicine, veterinary medicine, public health, and diagnostic laboratories and it will be especially helpful for those who are not experts in the field.
Paperback, 456 pages, full-color illustrations.

Zoonoses: Infectious Diseases Transmissible from Animals to Humans, Third Edition

Gene 4 of Marburg virus, strain Musoke, was subjected to nucleotide sequence analysis. It is 2,844 nucleotides long and extends from genome position 5821 to position 8665 (EMBL Data Library, emnew: MVREPCYC [accession no. Z12132]). The gene is flanked by transcriptional signal sequences (start signal, 3'-UACUUCUUGUAAUU-5'; termination signal, 3'-UAAUUCUUUUU-5') which are conserved in all Marburg virus genes. The major open reading frame encodes a polypeptide of 681 amino acids (M(r), 74,797). After in vitro transcription and translation, as well as expression in Escherichia coli, this protein was identified by its immunoreactivity with specific antisera as the unglycosylated form of the viral membrane glycoprotein (GP). The GP is characterized by the following four different domains: (i) a hydrophobic signal peptide at the amino terminus (1 to 18), (ii) a predominantly hydrophilic external domain (19 to 643), (iii) a hydrophobic transmembrane anchor (644 to 673), and (iv) a small hydrophilic cytoplasmic tail at the carboxy terminus (674 to 681). Amino acid analysis indicated that the signal peptide is removed from the mature GP. The GP therefore has the structural features of a type I transmembrane glycoprotein. The external domain of the protein has 19 N-glycosylation sites and several clusters of hydroxyamino acids and proline residues that are likely to be the attachment sites for about 30 O-glycosidic carbohydrate chains. The region extending from positions 585 to 610 shows significant homology to a domain observed in the envelope proteins of several retroviruses and Ebola virus that has been suspected to be responsible for immunosuppressive properties of these viruses. A second open reading frame of gene 4 has the coding capacity for an unidentified polypeptide 112 amino acids long.

Werner Slenczka

Papers

Glycosylation and oligomerization of the spike protein of marburg virus

Zoonoses: Infectious Diseases Transmissible from Animals to Humans

Release of Viral Glycoproteins during Ebola Virus Infection

Zoonoses: Infectious Diseases Transmissible from Animals to Humans, Third Edition

Marburg virus gene 4 encodes the virion membrane protein, a type I transmembrane glycoprotein.