bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and Immunological Insights on Severe, Adverse Neurotropic and Viscerotropic Disease following 17D Yellow Fever Vaccination
Authors: Silva Maria Luiza , Espírito-Santo Luçandra Ramos , Martins Marina Angela , Silveira-Lemos Denise , Peruhype-Magalhães Vanessa , Caminha Ricardo Carvalho , de Andrade Maranhão-Filho Péricles , Auxiliadora-Martins Maria , de Menezes Martins Reinaldo , Galler Ricardo , da Silva Freire Marcos , Marcovistz Rugimar , Homma Akira , Teuwen Dirk E. , Elói-Santos Silvana Maria , Andrade Mariléia Chaves , Teixeira-Carvalho Andréa , Martins-Filho Olindo Assis 
Published: November 2009

ABSTRACT

Yellow fever (YF) vaccines (17D-204 and 17DD) are well tolerated and cause very low rates of severe adverse events (YEL-SAE), such as serious allergic reactions, neurotropic adverse diseases (YEL-AND), and viscerotropic diseases (YEL-AVD). Viral and host factors have been postulated to explain the basis of YEL-SAE. However, the mechanisms underlying the occurrence of YEL-SAE remain unknown. The present report provides a detailed immunological analysis of a 23-year-old female patient. The patient developed a suspected case of severe YEL-AVD with encephalitis, as well as with pancreatitis and myositis, following receipt of a 17D-204 YF vaccination. The patient exhibited a decreased level of expression of Fc-γR in monocytes (CD16, CD32, and CD64), along with increased levels of NK T cells (an increased CD3
+
CD16
+/−
CD56
+/−
/CD3
+
ratio), activated T cells (CD4
+
and CD8
+
cells), and B lymphocytes. Enhanced levels of plasmatic cytokines (interleukin-6 [IL-6], IL-17, IL-4, IL-5, and IL-10) as well as an exacerbated
ex vivo
intracytoplasmic cytokine pattern, mainly observed within NK cells (gamma interferon positive [IFN-γ
+
], tumor necrosis factor alpha positive [TNF-α
+
], and IL-4 positive [IL-4
+
]), CD8
+
T cells (IL-4
+
and IL-5
+
), and B lymphocytes (TNF-α
+
, IL-4
+
, and IL-10
+
). The analysis of CD4
+
T cells revealed a complex profile that consisted of an increased frequency of IL-12
+
and IFN-γ
+
cells and a decreased percentage of TNF-α
+
, IL-4
+
, and IL-5
+
cells. Depressed cytokine synthesis was observed in monocytes (TNF-α
+
) following the provision of antigenic stimuli
in vitro
. These results support the hypothesis that a strong adaptive response and abnormalities in the innate immune system may be involved in the establishment of YEL-AND and YEL-AVD.
Kinetics of Antibody Persistence following Administration of a Combination Meningococcal Serogroup C and
Haemophilus influenzae
Type b Conjugate Vaccine in Healthy Infants in the United Kingdom Primed with a Monovalent Meningococcal Serogroup C Vaccine
Authors: Borrow Ray , Andrews Nick , Findlow Helen , Waight Pauline , Southern Joanna , Crowley-Luke Annette , Stapley Lorraine , England Anna , Findlow Jamie , Miller Elizabeth 
Published: November 2009

ABSTRACT

The kinetics of antibody persistence following the administration of a combination meningococcal serogroup C and
Haemophilus influenzae
type b (Hib) conjugate vaccine (Menitorix) in the second year of life in children primed with two doses of one of three monovalent meningococcal serogroup C (MCC) vaccines was investigated. The study subjects were administered either Menitorix at 12 to 15 months of age, followed by the seven-valent pneumococcal conjugate vaccine (PCV7) and the measles, mumps, and rubella vaccine 4 to 6 weeks later, or all three vaccines concomitantly at 12 to 15 months of age. Blood samples were collected before and 1, 2, 12, and 24 months after the boosting. Sera were analyzed for meningococcal serogroup C serum bactericidal antibody (SBA) and IgG as well as Hib-polyribosylribitol phosphate (PRP)-specific IgG. The antibody persistence data from this study were compared to those of a prior study of Southern et al. (Clin. Vaccine Immunol. 14:1328-1333, 2007) in which children were given three primary doses of a vaccine containing both the MCC and the Hib vaccines but were boosted only with a Hib conjugate vaccine. The magnitude of the meningococcal SBA geometric mean titer was higher for those subjects primed with the MCC vaccine conjugated to tetanus toxoid (NeisVac-C) than for those primed with one of two MCC vaccines conjugated to CRM
197
(Menjugate or Meningitec) up to 1 year following boosting. Two years after boosting, the percentages of subjects with putatively protective SBA titers of ≥8 for children primed with NeisVac-C, Menjugate, and Meningitec were 43%, 22%, and 23%, respectively. Additional booster doses of the MCC vaccine may be required in the future to maintain good antibody levels; however, there is no immediate need for a booster during adolescence, as mathematical modeling has shown that persisting herd immunity is likely to control disease for a number of years.
HIV-Selectest Enzyme Immunoassay and Rapid Test: Ability To Detect Seroconversion following HIV-1 Infection
Authors: Khurana Surender , Norris Philip J. , Busch Michael P. , Haynes Barton F. , Park Susan , Sasono Pretty , Mlisana Koleka , Salim Abdool Karim , Hecht Frederick M. , Mulenga Joseph , Chomba Elwyn , Hunter Eric , Allen Susan , Nemo George , Rodriguez-Chavez Isaac R. , Margolick Joseph B. , Golding Hana 
Published: November 2009

ABSTRACT
HIV-Selectest is a serodiagnostic enzyme immunoassay (EIA), containing p6 and gp41 peptides, designed to differentiate between vaccine-induced antibodies and true infections. A rapid test version of the HIV-Selectest was developed. Both assays detected HIV antibodies in men and women within 2 to 4 weeks of infection, with sensitivity similar to third-generation EIAs.
GC Content-Based Pan-Pox Universal PCR Assays for Poxvirus Detection
Authors: Li Yu , Meyer Hermann , Zhao Hui , Damon Inger K. 
Published: November 2009

ABSTRACT

Chordopoxviruses of the subfamily
Chordopoxvirinae
, family
Poxviridae
, infect vertebrates and consist of at least eight genera with broad host ranges. For most chordopoxviruses, the number of viral genes and their relative order are highly conserved in the central region. The GC content of chordopoxvirus genomes, however, evolved into two distinct types: those with genome GC content of more than 60% and those with a content of less than 40% GC. Two standard PCR assays were developed to identify chordopoxviruses based on whether the target virus has a low or high GC content. In design of the assays, the genus
Avipoxvirus
, which encodes major rearrangements of gene clusters, was excluded. These pan-pox assays amplify DNA from more than 150 different isolates and strains, including from primary clinical materials, from all seven targeted genera of chordopoxviruses and four unclassified new poxvirus species. The pan-pox assays represent an important advance for the screening and diagnosis of human and animal poxvirus infections, and the technology used is accessible to many laboratories worldwide.
Broadly Neutralizing Monoclonal Antibodies 2F5 and 4E10 Directed against the Human Immunodeficiency Virus Type 1 gp41 Membrane-Proximal External Region Protect against Mucosal Challenge by Simian-Human Immunodeficiency Virus SHIVBa-L
Authors: Hessell Ann J. , Rakasz Eva G. , Tehrani David M. , Huber Michael , Weisgrau Kimberly L. , Landucci Gary , Forthal Donald N. , Koff Wayne C. , Poignard Pascal , Watkins David I. , Burton Dennis R. 
Published: November 2009

ABSTRACTThe membrane-proximal external region (MPER) of HIV-1, located at the C terminus of the gp41 ectodomain, is conserved and crucial for viral fusion. Three broadly neutralizing monoclonal antibodies (bnMAbs), 2F5, 4E10, and Z13e1, are directed against linear epitopes mapped to the MPER, making this conserved region an important potential vaccine target. However, no MPER antibodies have been definitively shown to provide protection against HIV challenge. Here, we show that both MAbs 2F5 and 4E10 can provide complete protection against mucosal simian-human immunodeficiency virus (SHIV) challenge in macaques. MAb 2F5 or 4E10 was administered intravenously at 50 mg/kg to groups of six male Indian rhesus macaques 1 day prior to and again 1 day following intrarectal challenge with SHIVBa-L. In both groups, five out of six animals showed complete protection and sterilizing immunity, while for one animal in each group a low level of viral replication following challenge could not be ruled out. The study confirms the protective potential of 2F5 and 4E10 and supports emphasis on HIV immunogen design based on the MPER region of gp41.
Structure of the Nucleoprotein Binding Domain of Mokola Virus Phosphoprotein
Authors: Assenberg René , Delmas Olivier , Ren Jingshan , Vidalain Pierre-Olivier , Verma Anil , Larrous Florence , Graham Stephen C. , Tangy Frédéric , Grimes Jonathan M. , Bourhy Hervé 
Published: November 2009

ABSTRACT

Mokola virus (MOKV) is a nonsegmented, negative-sense RNA virus that belongs to the
Lyssavirus
genus and
Rhabdoviridae
family. MOKV phosphoprotein P is an essential component of the replication and transcription complex and acts as a cofactor for the viral RNA-dependent RNA polymerase. P recruits the viral polymerase to the nucleoprotein-bound viral RNA (N-RNA) via an interaction between its C-terminal domain and the N-RNA complex. Here we present a structure for this domain of MOKV P, obtained by expression of full-length P in
Escherichia coli
, which was subsequently truncated during crystallization. The structure has a high degree of homology with P of rabies virus, another member of
Lyssavirus
genus, and to a lesser degree with P of vesicular stomatitis virus (VSV), a member of the related
Vesiculovirus
genus. In addition, analysis of the crystal packing of this domain reveals a potential binding site for the nucleoprotein N. Using both site-directed mutagenesis and yeast two-hybrid experiments to measure P-N interaction, we have determined the relative roles of key amino acids involved in this interaction to map the region of P that binds N. This analysis also reveals a structural relationship between the N-RNA binding domain of the P proteins of the
Rhabdoviridae
and the
Paramyxoviridae
.
Nuclear Import and Assembly of Influenza A Virus RNA Polymerase Studied in Live Cells by Fluorescence Cross-Correlation Spectroscopy
Authors: Huet Sébastien , Avilov Sergiy V. , Ferbitz Lars , Daigle Nathalie , Cusack Stephen , Ellenberg Jan 
Published: November 2009

ABSTRACT
Intracellular transport and assembly of the subunits of the heterotrimeric RNA-dependent RNA polymerase constitute a key component of the replication cycle of influenza virus. Recent results suggest that efficient polymerase assembly is a limiting factor in the viability of reassortant viruses. The mechanism of nuclear import and assembly of the three polymerase subunits, PB1, PB2, and PA, is still controversial, yet it is clearly of great significance in understanding the emergence of new strains with pandemic potential. In this study, we systematically investigated the interactions between the polymerase subunits and their localization in living cells by fluorescence cross-correlation spectroscopy (FCCS) and quantitative confocal microscopy. We could show that PB1 and PA form a dimer in the cytoplasm, which is imported into the nucleus separately from PB2. Once in the nucleus, the PB1/PA dimer associates with PB2 to form the trimeric polymerase. Photon-counting histogram analysis revealed that trimeric polymerase complexes can form higher-order oligomers in the nucleus. We furthermore demonstrate that impairing the nuclear import of PB2 by mutating its nuclear localization signal leads to abnormal formation of the trimeric polymerase in the cytoplasm. Taken together, our results demonstrate which of the previously discussed influenza virus polymerase transport models operates in live cells. Our study sheds light on the interplay between the nuclear import of the subunits and the assembly of the influenza virus polymerase and provides a methodological framework to analyze the effects of different host range mutations in the future.
Chimeric Feline Coronaviruses That Encode Type II Spike Protein on Type I Genetic Background Display Accelerated Viral Growth and Altered Receptor Usage
Authors: Tekes Gergely , Hofmann-Lehmann Regina , Bank-Wolf Barbara , Maier Reinhard , Thiel Heinz-Jürgen , Thiel Volker 
Published: November 2009

ABSTRACT
Persistent infection of domestic cats with feline coronaviruses (FCoVs) can lead to a highly lethal, immunopathological disease termed feline infectious peritonitis (FIP). Interestingly, there are two serotypes, type I and type II FCoVs, that can cause both persistent infection and FIP, even though their main determinant of host cell tropism, the spike (S) protein, is of different phylogeny and displays limited sequence identity. In cell culture, however, there are apparent differences. Type II FCoVs can be propagated to high titers by employing feline aminopeptidase N (fAPN) as a cellular receptor, whereas the propagation of type I FCoVs is usually difficult, and the involvement of fAPN as a receptor is controversial. In this study we have analyzed the phenotypes of recombinant FCoVs that are based on the genetic background of type I FCoV strain Black but encode the type II FCoV strain 79-1146 S protein. Our data demonstrate that recombinant FCoVs expressing a type II FCoV S protein acquire the ability to efficiently use fAPN for host cell entry and corroborate the notion that type I FCoVs use another main host cell receptor. We also observed that recombinant FCoVs display a large-plaque phenotype and, unexpectedly, accelerated growth kinetics indistinguishable from that of type II FCoV strain 79-1146. Thus, the main phenotypic differences for type I and type II FCoVs in cell culture, namely, the growth kinetics and the efficient usage of fAPN as a cellular receptor, can be attributed solely to the FCoV S protein.
HIV Infection Is Associated with a Preferential Decline in Less-Differentiated CD56dimCD16+NK Cells
Authors: Hong Henoch S. , Eberhard Johanna M. , Keudel Phillip , Bollmann Benjamin A. , Ballmaier Matthias , Bhatnagar Nupur , Zielinska-Skowronek Margot , Schmidt Reinhold E. , Meyer-Olson Dirk 
Published: November 2009

ABSTRACTHIV-1 infection is characterized by loss of CD56dimCD16+NK cells and increased terminal differentiation on various lymphocyte subsets. We identified a decrease of CD57−and CD57dimcells but not of CD57brightcells on CD56dimCD16+NK cells in chronic HIV infection. Increasing CD57 expression was strongly associated with increasing frequencies of killer immunoglobulin-like receptors (KIRs) and granzyme B-expressing cells but decreasing percentages of cells expressing CD27+, HLA-DR+, Ki-67+, and CD107a. Our data indicate that HIV leads to a decline of less-differentiated cells and suggest that CD57 is a useful marker for terminal differentiation on NK cells.
Viral Mutagenesis as a Means for Generating Novel Proteins
Authors: Davis John N. , van den Pol Anthony N. 
Published: November 2009

ABSTRACT
We demonstrate that a mutation-prone virus engineered to express a foreign gene is an expedient means for generating novel mutant nonviral proteins in mammalian cells. Using vesicular stomatitis virus to express a gene coding for a fluorescent DsRed protein, a number of green mutant variants including a new variant not previously described were rapidly isolated from infected cells, sequenced, and cloned. Similar methods may be useful in the development of physiologically sensitive fluorescent reporter proteins and directed evolution or mutagenesis of proteins in general.
Androgen Stimulates Transcription and Replication of Xenotropic Murine Leukemia Virus-Related Virus
Authors: Dong Beihua , Silverman Robert H. 
Published: November 2009

ABSTRACT
Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus originally identified in a subset of prostate cancer patients. Because androgens stimulate prostate tumors and some retroviruses, we investigated the effects of dihydrotestosterone (DHT) on XMRV transcription and replication. Transcription from the XMRV U3 region was stimulated up to 2-fold by DHT, but only in cells containing a functional androgen receptor. Mutations in the glucocorticoid response element (GRE) of XMRV impaired basal transcription and androgen responsiveness. Furthermore, DHT stimulated XMRV replication 3-fold, whereas androgen inhibitors (casodex and flutamide) suppressed viral growth up to 3-fold. Findings suggest that integration of the XMRV long terminal repeat (LTR) into host DNA could impart androgen stimulation on cellular genes.
A Single-Dose Influenza A (H5N1) Vaccine Safe and Immunogenic in Adult and Elderly Patients: an Approach to Pandemic Vaccine Development
Authors: Vajo Zoltan , Wood John , Kosa Lajos , Szilvasy Istvan , Paragh Gyorgy , Pauliny Zsuzsanna , Bartha Kálmán , Visontay Ildiko , Kis Agnes , Jankovics Istvan 
Published: November 2009

ABSTRACT
With the ongoing pandemic of influenza A (H1N1) virus infection and the threat of high fatality rates for recent human cases of infection with highly pathogenic H5N1 strains, there has been considerable interest in developing pandemic vaccines. Here we report a randomized multicenter dose-finding clinical trial of a whole-virion, inactivated, adjuvanted H5N1 vaccine in adult and elderly volunteers. Four hundred eighty patients were randomly assigned to receive one or two doses of 3.5 μg of the vaccine or one dose of 6 or 12 μg. The subjects were monitored for safety analysis, and serum samples were obtained to assess immunogenicity by hemagglutination inhibition and microneutralization tests. The subjects developed antibody responses against the influenza A (H5N1) virus. Single doses of ≥6 μg fulfilled EU and U.S. licensing criteria for interpandemic and pandemic influenza vaccines. Except for occasional injection site pain, malaise, and fever, no adverse events were observed. We found that the present vaccine is safe and immunogenic in healthy adult and elderly subjects and requires low doses and, unlike any other H5N1 vaccines, only one injection to trigger immune responses which comply with licensing criteria. A vaccine using the same methods as those described in this report, but based on a wild-type swine-origin 2009 (H1N1) influenza A virus isolate from the United States (supplied by the CDC), has been developed and is currently being tested by our group.
Papillomavirus Prophylactic Vaccines: Established Successes, New Approaches
Authors: Campo M. Saveria , Roden Richard B. S. 
Published: November 2009

ABSTRACT
Vaccines against the human papillomaviruses (HPVs) most frequently associated with cancer of the cervix are now available. These prophylactic vaccines, based on virus-like particles (VLPs), are extremely effective, providing protection from infection in almost 100% of cases. However, the vaccines present some limitations: they are effective primarily against the HPV type present in the vaccine, are expensive to produce, and need a cold chain. Vaccines based on the minor capsid protein L2 have been very successful in animal models and have been shown to provide a good level of protection against different papillomavirus types. The potential of L2-based vaccines to protect against many types of HPVs is discussed.
NS1′ of Flaviviruses in the Japanese Encephalitis Virus Serogroup Is a Product of Ribosomal Frameshifting and Plays a Role in Viral Neuroinvasiveness
Authors: Melian Ezequiel Balmori , Hinzman Edward , Nagasaki Tomoko , Firth Andrew E. , Wills Norma M. , Nouwens Amanda S. , Blitvich Bradley J. , Leung Jason , Funk Anneke , Atkins John F. , Hall Roy , Khromykh Alexander A. 
Published: November 2009

ABSTRACT
Flavivirus NS1 is a nonstructural protein involved in virus replication and regulation of the innate immune response. Interestingly, a larger NS1-related protein, NS1′, is often detected during infection with the members of the Japanese encephalitis virus serogroup of flaviviruses. However, how NS1′ is made and what role it performs in the viral life cycle have not been determined. Here we provide experimental evidence that NS1′ is the product of a −1 ribosomal frameshift event that occurs at a conserved slippery heptanucleotide motif located near the beginning of the NS2A gene and is stimulated by a downstream RNA pseudoknot structure. Using site-directed mutagenesis of these sequence elements in an infectious clone of the Kunjin subtype of West Nile virus, we demonstrate that NS1′ plays a role in viral neuroinvasiveness.
Herpes Simplex Virus Tegument ICP0 Is Capsid Associated, and Its E3 Ubiquitin Ligase Domain Is Important for Incorporation into Virions
Authors: Delboy Mark G. , Siekavizza-Robles Carlos R. , Nicola Anthony V. 
Published: November 2009

ABSTRACT
Herpes simplex virus (HSV) immediate-early (IE) protein ICP0 is a multifunctional regulator of HSV infection. ICP0 that is present in the tegument layer has not been well characterized. Protein compositions of wild-type and ICP0 null virions were similar, suggesting that the absence of ICP0 does not grossly impair virion assembly. ICP0 has a RING finger domain with E3 ubiquitin ligase activity that is necessary for IE functions. Virions with mutations in this domain contained greatly reduced levels of tegument ICP0, suggesting that the domain influences the incorporation of ICP0. Virion ICP0 was resistant to removal by detergent and salt and was associated with capsids, features common to inner tegument proteins.
Molecular Epidemiology of Simian Immunodeficiency Virus Infection in Wild-Living Gorillas
Authors: Neel Cécile , Etienne Lucie , Li Yingying , Takehisa Jun , Rudicell Rebecca S. , Ndong Bass Innocent , Moudindo Joseph , Mebenga Aimé , Esteban Amandine , Van Heuverswyn Fran , Liegeois Florian , Kranzusch Philip J. , Walsh Peter D. , Sanz Crickette M. , Morgan David B. , Ndjango Jean-Bosco N. , Plantier Jean-Christophe , Locatelli Sabrina , Gonder Mary K. , Leendertz Fabian H. , Boesch Christophe , Todd Angelique , Delaporte Eric , Mpoudi-Ngole Eitel , Hahn Beatrice H. , Peeters Martine 
Published: November 2009

ABSTRACT

Chimpanzees and gorillas are the only nonhuman primates known to harbor viruses closely related to HIV-1. Phylogenetic analyses showed that gorillas acquired the simian immunodeficiency virus SIVgor from chimpanzees, and viruses from the SIVcpz/SIVgor lineage have been transmitted to humans on at least four occasions, leading to HIV-1 groups M, N, O, and P. To determine the geographic distribution, prevalence, and species association of SIVgor, we conducted a comprehensive molecular epidemiological survey of wild gorillas in Central Africa. Gorilla fecal samples were collected in the range of western lowland gorillas (
n
= 2,367) and eastern Grauer gorillas (
n
= 183) and tested for SIVgor antibodies and nucleic acids. SIVgor antibody-positive samples were identified at 2 sites in Cameroon, with no evidence of infection at 19 other sites, including 3 in the range of the Eastern gorillas. In Cameroon, based on DNA and microsatellite analyses of a subset of samples, we estimated the prevalence of SIVgor to be 1.6% (range, 0% to 4.6%), which is significantly lower than the prevalence of SIVcpz
Ptt
in chimpanzees (5.9%; range, 0% to 32%). All newly identified SIVgor strains formed a monophyletic lineage within the SIVcpz radiation, closely related to HIV-1 groups O and P, and clustered according to their field site of origin. At one site, there was evidence for intergroup transmission and a high intragroup prevalence. These isolated hot spots of SIVgor-infected gorilla communities could serve as a source for human infection. The overall low prevalence and sporadic distribution of SIVgor could suggest a decline of SIVgor in wild populations, but it cannot be excluded that SIVgor is still more prevalent in other parts of the geographical range of gorillas.