bluuebunny/crossref_metadata_2025_split huggingface dataset:
Passive Sexual Transmission of Human Immunodeficiency Virus Type 1 Variants and Adaptation in New Hosts
Authors: Frater A. J. , Edwards C. T. T. , McCarthy N. , Fox J. , Brown H. , Milicic A. , Mackie N. , Pillay T. , Drijfhout J. W. , Dustan S. , Clarke J. R. , Holmes E. C. , Zhang H. T. , Pfafferott K. , Goulder P. J. , McClure M. O. , Weber J. , Phillips R. E. , Fidler S. 
Published: June 2006

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) genetic diversity is a major obstacle for the design of a successful vaccine. Certain viral polymorphisms encode human leukocyte antigen (HLA)-associated immune escape, potentially overcoming limited vaccine protection. Although transmission of immune escape variants has been reported, the overall extent to which this phenomenon occurs in populations and the degree to which it contributes to HIV-1 viral evolution are unknown. Selection on the HIV-1
env
gene at transmission favors neutralization-sensitive variants, but it is not known to what degree selection acts on the internal HIV-1 proteins to restrict or enhance the transmission of immune escape variants. Studies have suggested that HLA class I may determine susceptibility to HIV-1 infection, but a definitive role for HLA at transmission remains unproven. Comparing populations of acute seroconverters and chronically infected patients, we found no evidence of selection acting to restrict transmission of HIV-1 variants. We found that statistical associations previously reported in chronic infection between viral polymorphisms and HLA class I alleles are not present in acute infection, suggesting that the majority of viral polymorphisms in these patients are the result of transmission rather than de novo adaptation. Using four episodes of HIV-1 transmission in which the donors and recipients were both sampled very close to the time of infection we found that, despite a transmission bottleneck, genetic variants of HIV-1 infection are transmitted in a frequency-dependent manner. As HIV-1 infections are seeded by unique donor-adapted viral variants, each episode is a highly individual antigenic challenge. Host-specific, idiosyncratic HIV-1 antigenic diversity will seriously tax the efficacy of immunization based on consensus sequences.
Involvement of Novel Human Immunodeficiency Virus Type 1 Reverse Transcriptase Mutations in the Regulation of Resistance to Nucleoside Inhibitors
Authors: Svicher Valentina , Sing Tobias , Santoro Maria Mercedes , Forbici Federica , Rodríguez-Barrios Fátima , Bertoli Ada , Beerenwinkel Niko , Bellocchi Maria Concetta , Gago Federigo , d'Arminio Monforte Antonella , Antinori Andrea , Lengauer Thomas , Ceccherini-Silberstein Francesca , Perno Carlo Federico 
Published: June 2006

ABSTRACTWe characterized 16 additional mutations in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) whose role in drug resistance is still unknown by analyzing 1,906 plasma-derived HIV-1 subtype Bpolsequences from 551 drug-naïve patients and 1,355 nucleoside RT inhibitor (NRTI)-treated patients. Twelve mutations positively associated with NRTI treatment strongly correlated both in pairs and in clusters with known NRTI resistance mutations on divergent evolutionary pathways. In particular, T39A, K43E/Q, K122E, E203K, and H208Y clustered with the nucleoside analogue mutation 1 cluster (NAM1; M41L+L210W+T215Y). Their copresence in this cluster was associated with an increase in thymidine analogue resistance. Moreover, treatment failure in the presence of K43E, K122E, or H208Y was significantly associated with higher viremia and lower CD4 cell count. Differently, D218E clustered with the NAM2 pathway (D67N+K70R+K219Q+T215F), and its presence in this cluster determined an increase in zidovudine resistance. In contrast, three mutations (V35I, I50V, and R83K) negatively associated with NRTI treatment showed negative correlations with NRTI resistance mutations and were associated with increased susceptibility to specific NRTIs. In particular, I50V negatively correlated with the lamivudine-selected mutation M184V and was associated with a decrease in M184V/lamivudine resistance, whereas R83K negatively correlated with both NAM1 and NAM2 clusters and was associated with a decrease in thymidine analogue resistance. Finally, the association pattern of the F214L polymorphism revealed its propensity for the NAM2 pathway and its strong negative association with the NAM1 pathway. Our study provides evidence of novel RT mutational patterns that regulate positively and/or negatively NRTI resistance and strongly suggests that other mutations beyond those currently known to confer resistance should be considered for improved prediction of clinical response to antiretroviral drugs.
Cross-Clade Neutralizing Activity of Human Anti-V3 Monoclonal Antibodies Derived from the Cells of Individuals Infected with Non-B Clades of Human Immunodeficiency Virus Type 1
Authors: Gorny Miroslaw K. , Williams Constance , Volsky Barbara , Revesz Kathy , Wang Xiao-Hong , Burda Sherri , Kimura Tetsuya , Konings Frank A. J. , Nádas Arthur , Anyangwe Christopher A. , Nyambi Phillipe , Krachmarov Chavdar , Pinter Abraham , Zolla-Pazner Susan 
Published: June 2006

ABSTRACTThe majority of global human immunodeficiency virus infections are caused by viruses characterized by a GPGQ motif at the tip of the V3 loop. Characterization of anti-V3 monoclonal antibodies (MAbs) that neutralize isolates with the GPGQ V3 motif is an important step in designing vaccines that will induce such Abs. Consequently, seven human anti-V3 MAbs derived from the cells of individuals infected with non-B-subtype viruses (anti-V3non-BMAbs) were generated from the cells of individuals from Africa infected with circulating recombinant forms CRF02_AG, CRF09_cpx, and CRF13_cpx, each of which contains a subtype Aenvgene. Sequence analysis of plasma viruses revealed a GPGQ motif at the apex of the V3 loop from six of the seven subjects and a GPGR motif from one subject. The MAbs were selected with fusion proteins (FP) containing V392UG037.8or V3JR-CSFfrom subtype A or B, respectively. In virus binding assays, five of the seven (71%) anti-V3non-BMAbs bound to V3-FPs from both subtype A and subtype B, while only four of the nine (44%) anti-V3BMAbs recognized both V3-FPs. Using two neutralization assays, both the anti-V3non-Band the anti-V3BMAbs neutralized subtype B viruses with similar activities, while the anti-V3non-BMAbs exhibited a tendency toward both increased potency and breadth of neutralization against non-B viruses compared to anti-V3BMAbs. Statistical significance was not achieved, due in large measure to the sizes of the MAb panels, but the overall pattern of data strongly suggests that viruses with the GPGQ motif at the tip of the V3 loop induce anti-V3 Abs with broader cross-neutralizing activity than do viruses with the GPGR motif.
Deregulation of eIF4E: 4E-BP1 in Differentiated Human Papillomavirus-Containing Cells Leads to High Levels of Expression of the E7 Oncoprotein
Authors: Oh Kwang-Jin , Kalinina Anna , Park No-Hee , Bagchi Srilata 
Published: June 2006

ABSTRACT
Infections with high-risk human papillomaviruses (HPVs) are linked to more than 95% of cervical cancers. HPVs replicate exclusively in differentiated cells and the function of the HPV E7 oncoprotein is essential for viral replication. In this study, we investigated the mechanism that regulates E7 expression in differentiated cells. The level of E7 protein was strongly induced in HPV-containing Caski, HOK-16B, and BaP-T cells during growth in methylcellulose-containing medium, a condition that induces differentiation. Enhanced expression of E7 was observed between 4 and 8 h of culturing in methylcellulose and was maintained for up to 24 h. The increase was not due to altered stability of the E7 protein or an increase in the steady-state level of the E7 mRNA. Instead, the translation of the E7 mRNA was enhanced during differentiation. More than 70 to 80% of the E7 mRNA was found in the polysome fractions in the differentiated cells. Consistent with this observation, higher levels of the phosphorylated translator inhibitor 4E-BP1 were observed in differentiated HPV-containing cells but not in differentiated non-HPV tumor cells or primary keratinocytes. The mTOR kinase inhibitor rapamycin blocked phosphorylation of 4E-BP1 and significantly decreased the level of E7 protein in Caski cells, suggesting that phosphorylation of 4E-BP1 is linked to E7 expression. Prevailing models for the molecular mechanisms underlying E7 expression have focused largely on transcriptional regulation. The results presented in this study demonstrate a significant role of the cellular translation machinery to maintain a high level of E7 protein in differentiated cells.
“Self” and “Nonself” Manipulation of Interferon Defense during Persistent Infection: Bovine Viral Diarrhea Virus Resists Alpha/Beta Interferon without Blocking Antiviral Activity against Unrelated Viruses Replicating in Its Host Cells
Authors: Schweizer Matthias , Mätzener Philippe , Pfaffen Gabriela , Stalder Hanspeter , Peterhans Ernst 
Published: June 2006

ABSTRACT

Bovine viral diarrhea virus
(BVDV), together with
Classical swine fever virus
(CSFV) and
Border disease virus
(BDV) of sheep, belongs to the genus
Pestivirus
of the
Flaviviridae
. BVDV is either cytopathic (cp) or noncytopathic (ncp), as defined by its effect on cultured cells. Infection of pregnant animals with the ncp biotype may lead to the birth of persistently infected calves that are immunotolerant to the infecting viral strain. In addition to evading the adaptive immune system, BVDV evades key mechanisms of innate immunity. Previously, we showed that ncp BVDV inhibits the induction of apoptosis and alpha/beta interferon (IFN-α/β) synthesis by double-stranded RNA (dsRNA). Here, we report that (i) both ncp and cp BVDV block the induction by dsRNA of the Mx protein (which can also be induced in the absence of IFN signaling); (ii) neither biotype blocks the activity of IFN; and (iii) once infection is established, BVDV is largely resistant to the activity of IFN-α/β but (iv) does not interfere with the establishment of an antiviral state induced by IFN-α/β against unrelated viruses. The results of our study suggest that, in persistent infection, BVDV is able to evade a central element of innate immunity directed against itself without generally compromising its activity against unrelated viruses (“nonself”) that may replicate in cells infected with ncp BVDV. This highly selective “self” and “nonself” model of evasion of the interferon defense system may be a key element in the success of persistent infection in addition to immunotolerance initiated by the early time point of fetal infection.
Cross-Subtype T-Cell Immune Responses Induced by a Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen
Authors: Weaver Eric A. , Lu Zhongjing , Camacho Zenaido T. , Moukdar Fatiha , Liao Hua-Xin , Ma Ben-Jiang , Muldoon Mark , Theiler James , Nabel Gary J. , Letvin Norman L. , Korber Bette T. , Hahn Beatrice H. , Haynes Barton F. , Gao Feng 
Published: June 2006

ABSTRACTThe genetic diversity among globally circulating human immunodeficiency virus type 1 (HIV-1) strains is a serious challenge for HIV-1 vaccine design. We have generated a synthetic group M consensusenvgene (CON6) for induction of cross-subtype immune responses and report here a comparative study of T-cell responses to this and natural strainenvimmunogens in a murine model. Three different strains of mice were immunized with CON6 as well as subtype A, B, or Cenvimmunogens, using a DNA prime-recombinant vaccinia virus boost strategy. T-cell epitopes were mapped by gamma interferon enzyme-linked immunospot analysis using five overlapping Env peptide sets from heterologous subtype A, B, and C viruses. The CON6-derived vaccine was immunogenic and induced a greater number of T-cell epitope responses than any single wild-type subtype A, B, and Cenvimmunogen and similar T-cell responses to a polyvalent vaccine. The responses were comparable to within-clade responses but significantly more than between-clade responses. The magnitude of the T-cell responses induced by CON6 (measured by individual epitope peptides) was also greater than the magnitude of responses induced by individual wild-typeenvimmunogens. Though the limited major histocompatibility complex repertoire in inbred mice does not necessarily predict responses in nonhuman primates and humans, these results suggest that synthetic centralizedenvimmunogens represent a promising approach for HIV-1 vaccine design that merits further characterization.
Humoral Responses against Coimmunized Protein Antigen but Not against Alphavirus-Encoded Antigens Require Alpha/Beta Interferon Signaling
Authors: Hidmark Åsa S. , Nordström Eva K. L. , Dosenovic Pia , Forsell Mattias N. E. , Liljeström Peter , Karlsson Hedestam Gunilla B. 
Published: June 2006

ABSTRACT

Viruses typically elicit potent adaptive immune responses, and live-virus-based vaccines are among the most efficient human vaccines known. The mechanisms by which viruses stimulate adaptive immune responses are not fully understood, but activation of innate immune signaling pathways in the early phase of the infection may be of importance. In addition to stimulating immune responses to viral antigens expressed in infected cells, viruses can also provide adjuvant signals to coimmunized protein antigens. Using recombinant Semliki Forest virus (rSFV)-based vaccines, we show that rSFV potently enhanced antibody responses against coimmunized protein antigens in the absence of other exogenously added adjuvants. Elicitation of antibody responses against both virus-encoded antigens and coimmunized protein antigens was independent of the signaling via Toll-like receptors (TLRs) previously implicated in antiviral responses. In contrast, the adjuvant effect of rSFV on coimmunized protein was completely abolished in mice lacking the alpha/beta interferon (IFN-α/β) receptor (IFN-AR1), demonstrating that IFN-α/β signaling was critical for mediating this effect. Antibody responses directed against virus-encoded antigens were intact in IFN-AR1
−/−
mice, suggesting that other signals are sufficient to drive immune responses against virally encoded antigens. These data provide a basis for the adjuvant effect of rSFV and show that different signals are required to stimulate antibody responses to virally encoded antigens and to antigens administered as purified protein vaccines, together with viral particles.
Evolutionary History of the Closely Related Group 2 Coronaviruses: Porcine Hemagglutinating Encephalomyelitis Virus, Bovine Coronavirus, and Human Coronavirus OC43
Authors: Vijgen Leen , Keyaerts Els , Lemey Philippe , Maes Piet , Van Reeth Kristien , Nauwynck Hans , Pensaert Maurice , Van Ranst Marc 
Published: June 2006

ABSTRACT
The close genetic and antigenic relatedness among the group 2 coronaviruses human coronavirus OC43 (HCoV-OC43), bovine coronavirus (BCoV), and porcine hemagglutinating encephalomyelitis virus (PHEV) suggests that these three viruses with different host specificities diverged fairly recently. In this study, we determined the complete genomic sequence of PHEV (strain PHEV-VW572), revealing the presence of a truncated group 2-specific ns2 gene in PHEV in comparison to other group 2 coronaviruses. Using a relaxed molecular clock approach, we reconstructed the evolutionary relationships between PHEV, BCoV, and HCoV-OC43 in real-time units, which indicated relatively recent common ancestors for these species-specific coronaviruses.
Distinct Roles for Nucleic Acid in In Vitro Assembly of Purified Mason-Pfizer Monkey Virus CANC Proteins
Authors: Ulbrich Pavel , Haubova Sarka , Nermut Milan V. , Hunter Eric , Rumlova Michaela , Ruml Tomas 
Published: June 2006

ABSTRACT
In contrast to other retroviruses, Mason-Pfizer monkey virus (M-PMV) assembles immature capsids in the cytoplasm. We have compared the ability of minimal assembly-competent domains from M-PMV and human immunodeficiency virus type 1 (HIV-1) to assemble in vitro into virus-like particles in the presence and absence of nucleic acids. A fusion protein comprised of the capsid and nucleocapsid domains of Gag (CANC) and its N-terminally modified mutant (ΔProCANC) were used to mimic the assembly of the viral core and immature particles, respectively. In contrast to HIV-1, where CANC assembled efficiently into cylindrical structures, the same domains of M-PMV were assembly incompetent. The addition of RNA or oligonucleotides did not complement this defect. In contrast, the M-PMV ΔProCANC molecule was able to assemble into spherical particles, while that of HIV-1 formed both spheres and cylinders. For M-PMV, the addition of purified RNA increased the efficiency with which ΔProCANC formed spherical particles both in terms of the overall amount and the numbers of completed spheres. The amount of RNA incorporated was determined, and for both rRNA and MS2-RNA, quantities similar to that of genomic RNA were encapsidated. Oligonucleotides also stimulated assembly; however, they were incorporated into ΔProCANC spherical particles in trace amounts that could not serve as a stoichiometric structural component for assembly. Thus, oligonucleotides may, through a transient interaction, induce conformational changes that facilitate assembly, while longer RNAs appear to facilitate the complete assembly of spherical particles.
Vaccinia Virus Intermediate and Late Promoter Elements Are Targeted by the TATA-Binding Protein
Authors: Knutson Bruce A. , Liu Xu , Oh Jaewook , Broyles Steven S. 
Published: June 2006

ABSTRACT
Vaccinia virus replicates in the cytoplasm of the host cell and encodes its own RNA polymerase and transcription factors. The proteins that target the poxvirus RNA polymerase to intermediate- and late-class promoters have not been identified. In this study, representatives of the intermediate and late promoters were characterized at the nucleotide level to identify essential motifs. Both intermediate and late viral promoters are shown to have an essential element suggestive of TATA boxes, which are potential targets for the TATA-binding protein (TBP). Several approaches were used to test for TBP requirement in vaccinia virus transcription, including overexpression of TBP, expression of a dominant negative mutant of TBP, RNA interference, and expression of adenovirus E1A protein, which inactivates TBP. In each case, the results support an essential role for TBP in vaccinia virus intermediate- and late-gene transcription. These findings indicate that poxviruses have integrated TBP as a central feature into an otherwise heterologous transcription system. A model for transcriptional switching, in which both intermediate and late promoter elements are targeted by TBP that recruits viral transcription factors to assemble a functional complex on their cognate promoters and a dysfunctional, repressed complex on the other class, is proposed.
Conformational States of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Ectodomain
Authors: Li Fang , Berardi Marcelo , Li Wenhui , Farzan Michael , Dormitzer Philip R. , Harrison Stephen C. 
Published: June 2006

ABSTRACT
The severe acute respiratory syndrome coronavirus enters cells through the activities of a spike protein (S) which has receptor-binding (S1) and membrane fusion (S2) regions. We have characterized four sequential states of a purified recombinant S ectodomain (S-e) comprising S1 and the ectodomain of S2. They are S-e monomers, uncleaved S-e trimers, cleaved S-e trimers, and dissociated S1 monomers and S2 trimer rosettes. Lowered pH induces an irreversible transition from flexible, L-shaped S-e monomers to clove-shaped trimers. Protease cleavage of the trimer occurs at the S1-S2 boundary; an ensuing S1 dissociation leads to a major rearrangement of the trimeric S2 and to formation of rosettes likely to represent clusters of elongated, postfusion trimers of S2 associated through their fusion peptides. The states and transitions of S suggest conformational changes that mediate viral entry into cells.
A prospective cohort study of injury in amateur and professional boxing
Authors: Zazryn T , Cameron P , McCrory P 
Published: June 2006

Background:There is concern over the potential for a high incidence of injury in boxing. This is despite a lack of prospective data evaluating the risk for modern day participants. Updated, reliable data with a focus on potential exposure to injury for both amateur and, especially, professional boxers is required.Aim:To determine the epidemiology of injury and exposure of amateur and professional boxers in Victoria, Australia.Methods:A prospective cohort study with one year follow up was carried out over 2004–2005. Thirty three amateur and 14 active professional boxers registered with either Boxing Victoria Inc (amateurs) or the Professional Boxing and Combat Sports Board of Victoria (professionals) volunteered. Exposure at training and competition was measured, and any injuries sustained during this participation were recorded.Results:Twenty one injuries were sustained by the cohort during the follow up period. Most were to the head region (71%; 95% confidence interval −3.7 to 89.4), with concussion being the most common (33%). An overall injury rate of 2.0 injuries per 1000 hours of boxing was calculated.Conclusion:The high exposure experienced by the boxers (as a result of considerable training time) indicated that boxing has acute injury rates comparable to, and often lower than, those found in other contact and non-contact sports. Further, acute injuries during training appear to be less common and severe than those sustained in bouts.
Tuberculosis outbreak among students in a boarding school
Authors: Stein-Zamir C. , Volovik I. , Rishpon S. , Atamna A. , Lavy A. , Weiler-Ravell D. 
Published: June 2006

Tuberculosis (TB) outbreaks present a public health challenge. Six cases of active TB emerged in a boarding school in Israel during 1 yr. An epidemiological outbreak investigation was performed, followed by implementation of control measures.The investigation included interviews, tuberculin skin test (TST) and chest radiographs of the students. Close contact (n = 155) was defined as being in the same class or dormitory with a patient. Remote contact (n = 246) was defined as being in the school.An epidemiological association was detected among five of the cases and a distinct pattern was found in molecular analysis. TST was performed in 398 (99.2%) students. Repeated (two-step) TST was applied to the close contacts. The degree of contact, country of origin and previous bacille Calmette–Guérin vaccination were significantly associated with TST reactions. Preventive directly observed therapy was completed by 157 (91.3%) students. During 5 yrs follow-up, no additional cases emerged.While investigating a tuberculosis outbreak, the definition of degree of contact is a significant predictor for detecting positive tuberculin test. Immigration from an endemic country, as well as previous bacille Calmette–Guérin vaccination have a major effect on tuberculin skin-test results. The directly observed therapy approach was found to be successful in preventing further morbidity.