bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-Kala-Azar Dermal Leishmaniasis in a Patient Treated with Injectable Paromomycin for Visceral Leishmaniasis in India
Authors: Pandey Krishna , Das V. N. R. , Singh Dharmendra , Das Sushmita , Lal C. S. , Verma N. , Bimal S. , Topno R. K. , Siddiqui N. A. , Verma R. B. , Sinha P. K. , Das Pradeep 
Published: January 2012

ABSTRACT
Post kala-azar dermal leishmaniasis (PKDL) is a skin manifestation that usually develops after treatment of visceral leishmaniasis (VL), a major public health problem in India. The diagnosis and management of PKDL is complex. This is the first case report from India in which PKDL occurred after paromomycin treatment for VL in an Indian patient.
Scalp Abscess Due to Streptomyces cacaoi subsp.
cacaoi
, First Report in a Human Infection
Authors: Pellegrini Gerald J. , Graziano James C. , Ragunathan Latha , Bhat Malini A. , Hemashettar Basavaraj M. , Brown June M. 
Published: January 2012

ABSTRACT

Streptomyces cacaoi
subsp.
cacaoi
, a Gram-positive, branching filamentous bacteria, was isolated from a scalp infection in a patient from Pondicherry, India. Phenotypic tests identified the isolate as a
Streptomyces
species, but 16S rRNA sequence analysis provided the species identification required for tracking of this emerging pathogen.
Role of Conserved Cysteine Residues in Hepatitis C Virus Glycoprotein E2 Folding and Function
Authors: McCaffrey Kathleen , Boo Irene , Tewierek Kevin , Edmunds Mark L. , Poumbourios Pantelis , Drummer Heidi E. 
Published: January 2012

ABSTRACT

Hepatitis C virus glycoprotein E2 contains 18 conserved cysteines predicted to form nine disulfide pairs. In this study, a comprehensive cysteine-alanine mutagenesis scan of all 18 cysteine residues was performed in E1E2-pseudotyped retroviruses (HCVpp) and recombinant E2 receptor-binding domain (E2 residues 384 to 661 [E2
661
]). All 18 cysteine residues were absolutely required for HCVpp entry competence. The phenotypes of individual cysteines and pairwise mutation of disulfides were largely the same for retrovirion-incorporated E2 and E2
661
, suggesting their disulfide arrangements are similar. However, the contributions of each cysteine residue and the nine disulfides to E2 structure and function varied. Individual Cys-to-Ala mutations revealed discordant effects, where removal of one Cys within a pair had minimal effect on H53 recognition and CD81 binding (C486 and C569) while mutation of its partner abolished these functions (C494 and C564). Removal of disulfides at C581-C585 and C452-C459 significantly reduced the amount of E1 coprecipitated with E2, while all other disulfides were absolutely required for E1E2 heterodimerization. Remarkably, E2
661
tolerates the presence of four free cysteines, as simultaneous mutation of C452A, C486A, C569A, C581A, C585A, C597A, and C652A (M+C597A) retained wild-type CD81 binding. Thus, only one disulfide from each of the three predicted domains, C429-C552 (DI), C503-C508 (DII), and C607-C644 (DIII), is essential for the assembly of the E2
661
CD81-binding site. Furthermore, the yield of total monomeric E2 increased to 70% in M+C597A. These studies reveal the contribution of each cysteine residue and the nine disulfide pairs to E2 structure and function.
Deletions in the Neuraminidase Stalk Region of H2N2 and H9N2 Avian Influenza Virus Subtypes Do Not Affect Postinfluenza Secondary Bacterial Pneumonia
Authors: Chockalingam Ashok K. , Hickman Danielle , Pena Lindomar , Ye Jianqiang , Ferrero Andrea , Echenique Jose R. , Chen Hongjun , Sutton Troy , Perez Daniel R. 
Published: January 2012

ABSTRACT

We investigated the synergism between influenza virus and
Streptococcus pneumoniae
, particularly the role of deletions in the stalk region of the neuraminidase (NA) of H2N2 and H9N2 avian influenza viruses. Deletions in the NA stalk (ΔNA) had no effect on NA activity or on the adherence of
S. pneumoniae
to virus-infected human alveolar epithelial (A549) and mouse lung adenoma (LA-4) cells, although it delayed virus elution from turkey red blood cells. Sequential
S. pneumoniae
infection of mice previously inoculated with isogenic recombinant H2N2 and H9N2 influenza viruses displayed severe pneumonia, elevated levels of intrapulmonary proinflammatory responses, and death. No differences between the WT and ΔNA mutant viruses were detected with respect to effects on postinfluenza pneumococcal pneumonia as measured by bacterial growth, lung inflammation, morbidity, mortality, and cytokine/chemokine concentrations. Differences were observed, however, in influenza virus-infected mice that were treated with oseltamivir prior to a challenge with
S. pneumoniae
. Under these circumstances, mice infected with ΔNA viruses were associated with a better prognosis following a secondary bacterial challenge. These data suggest that the H2N2 and H9N2 subtypes of avian influenza A viruses can contribute to secondary bacterial pneumonia and deletions in the NA stalk may modulate its outcome in the context of antiviral therapy.
Sangassou Virus, the First Hantavirus Isolate from Africa, Displays Genetic and Functional Properties Distinct from Those of Other Murinae-Associated Hantaviruses
Authors: Klempa Boris , Witkowski Peter T. , Popugaeva Elena , Auste Brita , Koivogui Lamine , Fichet-Calvet Elisabeth , Strecker Thomas , ter Meulen Jan , Krüger Detlev H. 
Published: January 2012

ABSTRACT

We have discovered the first indigenous African hantavirus, Sangassou virus (SANGV). The virus was isolated from an African wood mouse (
Hylomyscus simus
), trapped in a forest habitat in Guinea, West Africa. Here, we report on the characterization of the genetic and functional properties of the virus. The complete genome of SANGV was determined and showed typical hantavirus organization. The small (S), medium (M), and large (L) genome segments containing genes encoding nucleocapsid protein, two envelope glycoproteins, and viral polymerase were found to be 1,746, 3,650, and 6,531 nucleotides long, respectively. The exact 5′ and 3′ termini for all three segments of the SANGV genome were determined and were predicted to form the panhandle structures typical of bunyaviruses. Phylogenetic analyses of all three segment sequences confirmed SANGV as a
Murinae
-associated hantavirus most closely related to the European Dobrava-Belgrade virus. We showed, however, that SANGV uses β
1
integrin rather than β
3
integrin and decay-accelerating factor (DAF)/CD55 as an entry receptor. In addition, we demonstrated a strong induction of type III lambda interferon (IFN-λ) expression in type I IFN-deficient Vero E6 cells by SANGV. These properties are unique within
Murinae
-associated hantaviruses and make the virus useful in comparative studies focusing on hantavirus pathogenesis.
Adenosine Deaminase Acting on RNA 1 (ADAR1) Suppresses the Induction of Interferon by Measles Virus
Authors: Li Zhiqun , Okonski Kristina M. , Samuel Charles E. 
Published: January 2012

ABSTRACT

ADAR1, the interferon (IFN)-inducible adenosine deaminase acting on RNA, catalyzes the C-6 deamination of adenosine (A) to produce inosine (I) in RNA substrates with a double-stranded character. Because double-stranded RNA is a known inducer of IFN, we tested the role of ADAR1 in IFN induction following virus infection. HeLa cells made stably deficient in ADAR1 (ADAR1
kd
) were compared to vector control (CON
kd
) and protein kinase PKR-deficient (PKR
kd
) cells for IFN-β induction following infection with either parental (wild-type [WT]) recombinant Moraten vaccine strain measles virus (MV) or isogenic knockout mutants deficient for either V (V
ko
) or C (C
ko
) protein expression. We observed potent IFN-β transcript induction in ADAR1
kd
cells by all three viruses; in contrast, in ADAR1-sufficient CON
kd
cells, only the C
ko
mutant virus was an effective inducer and the IFN-β RNA induction was amplified by PKR. The enhanced IFN-β transcript-inducing capacity of the WT and V
ko
viruses seen in ADAR1-deficient cells correlated with the enhanced activation of PKR, IFN regulatory factor IRF3, and activator of transcription ATF2, reaching levels similar to those seen in C
ko
virus-infected cells. However, the level of IFN-β protein produced was not proportional to the level of IFN-β RNA but rather correlated inversely with the level of activated PKR. These results suggest that ADAR1 functions as an important suppressor of MV-mediated responses, including the activation of PKR and IRF3 and the induction of IFN-β RNA. Our findings further implicate a balanced interplay between PKR and ADAR1 in modulating IFN-β protein production following virus infection.
Correlation of Recombinant Integrase Activity and Functional Preintegration Complex Formation during Acute Infection by Replication-Defective Integrase Mutant Human Immunodeficiency Virus
Authors: Li Xiang , Koh Yasuhiro , Engelman Alan 
Published: January 2012

ABSTRACT

Previous studies characterized two types of replication-defective human immunodeficiency virus type 1 (HIV-1) integrase mutants: class I, which are specifically blocked at the integration step, and class II, which harbor additional virion production and/or reverse transcription defects. Class I mutant enzymes supported little if any metal ion-dependent 3′-processing and DNA strand transfer activities
in vitro
, whereas class II enzymes displayed partial or full catalytic function in studies with simplified assay designs, suggesting that defective interaction(s) with heterologous integrase binding proteins might underlie the class II mutant viral phenotype. To address this hypothesis, class I and II mutant enzymes were interrogated under expanded sets of
in vitro
conditions. The majority failed to catalyze the concerted integration of two viral DNA ends into target DNA, highlighting defective integrase function as the root cause of most class II in addition to all class I mutant virus infection defects. One mutant protein, K264E, in contrast, could support the wild-type level of concerted integration activity. After accounting for its inherent reverse transcription defect, HIV-1
K264E
moreover formed preintegration complexes that supported the efficient integration of endogenous viral DNA
in vitro
and normal levels and sequences of 2-long terminal repeat-containing circle junctions during acute infection. K264E integrase furthermore efficiently interacted
in vitro
with two heterologous binding partners, LEDGF/p75 and reverse transcriptase. Our results underscore the physiological relevance of concerted integration assays for tests of integrase mutant function and suggest that the K264E mutation disrupts an interaction with an intranuclear integrase binding partner that is important for HIV-1 integration.
An Antibody Recognizing the Apical Domain of Human Transferrin Receptor 1 Efficiently Inhibits the Entry of All New World Hemorrhagic Fever Arenaviruses
Authors: Helguera Gustavo , Jemielity Stephanie , Abraham Jonathan , Cordo Sandra M. , Martinez M. Guadalupe , Rodríguez José A. , Bregni Carlos , Wang Jinyize J. , Farzan Michael , Penichet Manuel L. , Candurra Nélida A. , Choe Hyeryun 
Published: January 2012

ABSTRACT
Five New World (NW) arenaviruses cause human hemorrhagic fevers. Four of these arenaviruses are known to enter cells by binding human transferrin receptor 1 (hTfR1). Here we show that the fifth arenavirus, Chapare virus, similarly uses hTfR1. We also identify an anti-hTfR1 antibody, ch128.1, which efficiently inhibits entry mediated by the glycoproteins of all five viruses, as well as replication of infectious Junín virus. Our data indicate that all NW hemorrhagic fever arenaviruses utilize a common hTfR1 apical-domain epitope and suggest that therapeutic agents targeting this epitope, including ch128.1 itself, can be broadly effective in treating South American hemorrhagic fevers.
Latent Kaposi's Sarcoma-Associated Herpesvirus Infection of Monocytes Downregulates Expression of Adaptive Immune Response Costimulatory Receptors and Proinflammatory Cytokines
Authors: Gregory Sean M. , Wang Ling , West John A. , Dittmer Dirk P. , Damania Blossom 
Published: January 2012

ABSTRACTKaposi's sarcoma-associated herpesvirus (KSHV) infection is associated with the development of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. We report the establishment of a monocytic cell line latently infected with KSHV (KSHV-THP-1). We profiled viral and cytokine gene expression in the KSHV-THP-1 cells compared to that in uninfected THP-1 cells and found that several genes involved in the host immune response were downregulated during latent infection, including genes for CD80, CD86, and the cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β). Thus, KSHV minimizes its immunological signature by suppressing key immune response factors, enabling persistent infection and evasion from host detection.
Analysis of Hepatitis C Virus Intrahost Diversity across the Coding Region by Ultradeep Pyrosequencing
Authors: Lauck Michael , Alvarado-Mora Mónica V. , Becker Ericka A. , Bhattacharya Dipankar , Striker Rob , Hughes Austin L. , Carrilho Flair J. , O'Connor David H. , Pinho João R. Rebello 
Published: January 2012

ABSTRACT
Hepatitis C virus (HCV) is the leading cause of liver disease worldwide. In this study, we analyzed four treatment-naïve patients infected with subtype 1a and performed Roche/454 pyrosequencing across the coding region. We report the presence of low-level drug resistance mutations that would most likely have been missed using conventional sequencing methods. The approach described here is broadly applicable to studies of viral diversity and could help to improve the efficacy of direct-acting antiviral agents (DAA) in the treatment of HCV-infected patients.
Activation of the Nipah Virus Fusion Protein in MDCK Cells Is Mediated by Cathepsin B within the Endosome-Recycling Compartment
Authors: Diederich Sandra , Sauerhering Lucie , Weis Michael , Altmeppen Hermann , Schaschke Norbert , Reinheckel Thomas , Erbar Stephanie , Maisner Andrea 
Published: January 2012

ABSTRACT
Proteolytic activation of the fusion protein of the highly pathogenic Nipah virus (NiV F) is a prerequisite for the production of infectious particles and for virus spread via cell-to-cell fusion. Unlike other paramyxoviral fusion proteins, functional NiV F activation requires endocytosis and pH-dependent cleavage at a monobasic cleavage site by endosomal proteases. Using prototype Vero cells, cathepsin L was previously identified to be a cleavage enzyme. Compared to Vero cells, MDCK cells showed substantially higher F cleavage rates in both NiV-infected and NiV F-transfected cells. Surprisingly, this could not be explained either by an increased F endocytosis rate or by elevated cathepsin L activities. On the contrary, MDCK cells did not display any detectable cathepsin L activity. Though we could confirm cathepsin L to be responsible for F activation in Vero cells, inhibitor studies revealed that in MDCK cells, cathepsin B was required for F-protein cleavage and productive replication of pathogenic NiV. Supporting the idea of an efficient F cleavage in early and recycling endosomes of MDCK cells, endocytosed F proteins and cathepsin B colocalized markedly with the endosomal marker proteins early endosomal antigen 1 (EEA-1), Rab4, and Rab11, while NiV F trafficking through late endosomal compartments was not needed for F activation. In summary, this study shows for the first time that endosomal cathepsin B can play a functional role in the activation of highly pathogenic NiV.
Rhesus Rotavirus Trafficking during Entry into MA104 Cells Is Restricted to the Early Endosome Compartment
Authors: Wolf Marie , Deal Emily M. , Greenberg Harry B. 
Published: January 2012

ABSTRACT
Endocytosis has recently been implicated in rotavirus (RV) entry. We examined the role of Rabs, which regulate endosomal trafficking, during RV entry. Several structural proteins of neuraminidase-sensitive and -insensitive RVs colocalized with Rab5, an early endosome marker, but not Rab7, a late endosome marker. Dominant-negative and constitutively active mutants demonstrated that Rab5 but not Rab4 or Rab7 affects rhesus RV (RRV) infectivity. These data suggest that early RRV trafficking is confined to the early endosome compartment and requires Rab5.
Expression of HERV-Fc1, a Human Endogenous Retrovirus, Is Increased in Patients with Active Multiple Sclerosis
Authors: Laska Magdalena Janina , Brudek Tomasz , Nissen Kari Konstantin , Christensen Tove , Møller-Larsen Anné , Petersen Thor , Nexø Bjørn Andersen 
Published: January 2012

ABSTRACTMultiple sclerosis (MS) is considered to be an autoimmune disease with an unknown cause and with immune system dysregulation. Among environmental factors, viruses are most often connected with the etiology of MS. Human endogenous retroviruses (HERVs) constitute 5 to 8% of human genomic DNA and have been detected as transcripts and proteins in the central nervous system (CNS) and peripheral blood, frequently in the context of neuroinflammation. HERV-Fc1, which belongs to the HERV-H/F family, has received our attention largely because of the genetic association with MS. We studied the expression of a capsid (Gag) protein of HERV-H/F origin by flow cytometry in peripheral blood mononuclear cells (PBMCs) from healthy controls and from MS patients with nonactive or active disease. There was a significant increase in HERV-H/F Gag expression in CD4+(P< 0.001) and CD8+(P< 0.001) T lymphocytes and in monocytes (P= 0.0356) in PBMCs from MS patients with active disease. Furthermore, we have undertaken the first rigorous SYBR green-based absolute quantitative PCR (Q-PCR) evaluation approach to quantify extracellular HERV-Fc1 RNA viral loads in plasma from MS patients and healthy controls. We found a 4-fold increase in extracellular HERV-Fc1 RNA titers in patients with active MS compared with healthy controls (P< 0.001). These findings strengthen the link between HERV-Fc1 and the pathology of MS. The cause and biological consequences of these differential expression levels will be the subject of further investigation. HERV-Fc1 biology could be a compelling area for understanding the pathology of MS and possibly other autoimmune disorders.
Analysis of the Autographa californica Multiple Nucleopolyhedrovirus Overlapping Gene Pair
lef3
and
ac68
Reveals that AC68 Is a
Per Os
Infectivity Factor and that LEF3 Is Critical, but Not Essential, for Virus Replication
Authors: Nie Yingchao , Fang Minggang , Erlandson Martin A. , Theilmann David A. 
Published: January 2012

ABSTRACT

Autographa californica
multiple nucleopolyhedrovirus
ac68
is a core gene that overlaps
lef3
which encodes the single-stranded DNA binding protein. A knockout (KO) virus lacking both
lef3
and
ac68
was generated (
lef3-ac68
2×KO) to enable the functional study of
ac68
. To produce an
ac68
KO virus that did not impact
lef3
expression, the
lef3-ac68
2×KO virus was repaired with a DNA fragment containing
lef3
and
ac68
, in which
ac68
contained point mutations so that only LEF3 was expressed. Repair of
lef3-ac68
2×KO with just
ac68
generated an
lef3
KO virus. Analysis of the a
c68
KO virus showed that viral DNA replication and budded virus (BV) levels were unaffected compared to levels in the double-repair or wild-type (WT) control virus. Bioassay analyses of
Trichoplusia ni
larvae injected with BV directly into the hemolymph, bypassing the gut, showed no difference in mortality rates between the
ac68
KO and the WT viruses. However, in oral bioassays the
ac68
KO occlusion bodies failed to kill larvae. These results show that the core gene
ac68
encodes a
per os
infectivity factor (
pif6
). The
lef3
KO virus was also analyzed, and virus replication was drastically reduced compared to WT virus, but very low levels of
lef3
KO virus DNA replication and BV production could be detected. In addition, in transfected cells P143 was transported to the nucleus in the absence of LEF3. This study therefore shows for the first time that even though the loss of LEF3 severely impairs virus replication, it is not absolutely essential for P143 nuclear import or viral replication.
Genome Sequence of Chinese Porcine Parvovirus Strain PPV2010
Authors: Cui Jin , Wang Xin , Ren Yudong , Cui Shangjin , Li Guangxing , Ren Xiaofeng 
Published: January 2012

ABSTRACT
Porcine parvovirus (PPV) isolate PPV2010 has recently emerged in China. Herein, we analyze the complete genome sequence of PPV2010. Our results indicate that the genome of PPV2010 bears mixed characteristics of virulent PPV and vaccine strains. Importantly, PPV2010 has the potential to be a naturally attenuated candidate vaccine strain.
Complete Genome Sequences of 138 Mycobacteriophages
Authors: Hatfull Graham F. ,   the Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science Program,   the KwaZulu-Natal Research Institute for Tuberculosis and HIV Mycobacterial Genetics Course Students,   the Phage Hunters Integrating Research and Education Program
Published: January 2012

ABSTRACT

Bacteriophages are the most numerous biological entities in the biosphere, and although their genetic diversity is high, it remains ill defined. Mycobacteriophages—the viruses of mycobacterial hosts—provide insights into this diversity as well as tools for manipulating
Mycobacterium tuberculosis
. We report here the complete genome sequences of 138 new mycobacteriophages, which—together with the 83 mycobacteriophages previously reported—represent the largest collection of phages known to infect a single common host,
Mycobacterium smegmatis
mc
2
155.
HLA B*5701-Positive Long-Term Nonprogressors/Elite Controllers Are Not Distinguished from Progressors by the Clonal Composition of HIV-Specific CD8
+
T Cells
Authors: Mendoza Daniel , Royce Cassandra , Ruff Laura E. , Ambrozak David R. , Quigley Máire F. , Dang Thurston , Venturi Vanessa , Price David A. , Douek Daniel C. , Migueles Stephen A. , Connors Mark 
Published: January 2012

ABSTRACT

To better understand the qualitative features of effective human immunodeficiency virus (HIV)-specific immunity, we examined the TCR clonal composition of CD8
+
T cells recognizing conserved HIV p24-derived epitopes in HLA-B*5701-positive long-term nonprogressors/elite controllers (LTNP/EC) and HLA-matched progressors. Both groups displayed oligoclonal HLA-B5701-restricted p24-specific CD8
+
T-cell responses with similar levels of diversity and few public clonotypes. Thus, HIV-specific CD8
+
T-cell responses in LTNP/EC are not differentiated from those of progressors on the basis of clonal diversity or TCR sharing.