Viruses

Research

22 pages, 294 KiB

Open AccessArticle

HIV-1 Subtype C Phylodynamics in the Global Epidemic

by Vlad Novitsky^1,2,*, Rui Wang³, Stephen Lagakos³ and Max Essex^1,2

¹ Department of Immunology and Infectious Diseases, Harvard School of Public Health AIDS Initiative, Harvard School of Public Health, Boston, MA, USA

² Botswana–Harvard AIDS Institute, Gaborone, Botswana

³ Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA

Viruses 2010, 2(1), 33-54; https://doi.org/10.3390/v2010033 - 7 Jan 2010

Cited by 23 | Viewed by 15175

Abstract

The diversity of HIV-1 and its propensity to generate escape mutants present fundamental challenges to control efforts, including HIV vaccine design. Intra-host diversification of HIV is determined by immune responses elicited by an HIV-infected individual over the course of the infection. Complex and [...] Read more.

The diversity of HIV-1 and its propensity to generate escape mutants present fundamental challenges to control efforts, including HIV vaccine design. Intra-host diversification of HIV is determined by immune responses elicited by an HIV-infected individual over the course of the infection. Complex and dynamic patterns of transmission of HIV lead to an even more complex population viral diversity over time, thus presenting enormous challenges to vaccine development. To address inter-patient viral evolution over time, a set of 653 unique HIV-1 subtype C gag sequences were retrieved from the LANL HIV Database, grouped by sampling year as <2000, 2000, 2001–2002, 2003, and 2004–2006, and analyzed for the site-specific frequency of translated amino acid residues. Phylogenetic analysis revealed that a total of 289 out of 653 (44.3%) analyzed sequences were found within 16 clusters defined by aLRT of more than 0.90. Median (IQR) inter-sample diversity of analyzed gag sequences was 8.7% (7.7%; 9.8%). Despite the heterogeneous origins of analyzed sequences, the gamut and frequency of amino acid residues in wild-type Gag were remarkably stable over the last decade of the HIV-1 subtype C epidemic. The vast majority of amino acid residues demonstrated minor frequency fluctuation over time, consistent with the conservative nature of the HIV-1 Gag protein. Only 4.0% (20 out of 500; HXB2 numbering) amino acid residues across Gag displayed both statistically significant (p<0.05 by both a trend test and heterogeneity test) changes in amino acid frequency over time as well as a range of at least 10% in the frequency of the major amino acid. A total of 59.2% of amino acid residues with changing frequency of 10%+ were found within previously identified CTL epitopes. The time of the most recent common ancestor of the HIV-1 subtype C was dated to around 1950 (95% HPD from 1928 to 1962). This study provides evidence for the overall stability of HIV-1 subtype C Gag among viruses circulating in the epidemic over the last decade. However selected sites across HIV-1C Gag with changing amino acid frequency are likely to be under selection pressure at the population level. Full article

(This article belongs to the Special Issue AIDS Vaccine)

▼ Show Figures

Figure 1

5 pages, 35 KiB

Open AccessCommunication

Preliminary Report on HIV-1 Vaccine Preparedness in Nigeria: Advantages of Recruiting University Students

by Abigail Edubio^1,†, Simon Agwale^1,‡, Marc Bulterys^2,§, Dadik Jelpe^3,||, John Idoko^4,¶, Chris Isichei⁵, Ruth Guyit⁶ and Alash’le Abimiku^7,*

¹ Laboratory of Leishmaniasis and AIDS, Department of Zoology, University of Jos, P.M.B 2084, Jos, Plateau State, Nigeria

² School of Medicine, University of New Mexico, Albuquerque, New Mexico, USA

³ Plateau State Human Virology Research Center (PLASVIREC), Plateau State Specialist Hospital, Jos, Nigeria

⁴ Faculty of Medical Sciences, University of Jos, P.M.B 2084 Jos, Plateau State, Nigeria

⁵ Department of Chemical Pathoglogy, University of Jos, P.M.B 2084 Jos, Plateau State, Nigeria

⁶ Institute of Education, University of Jos, P.M.B 2084 Jos, Plateau State, Nigeria

⁷ Division of Epidemiology and Prevention, Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, USA

^† Current address: P11 HIV-Variabilität und molekulare Epidemiologie, Robert Koch-Institut, Nordufer 20, 13353 Berlin, Germany.

^‡ Current address: Innovative Biotech Nig. Ltd., GRA Keffi, Nassarawa State, Nigeria.

^§ Current address: US Centers for Disease Control and Prevention Global AIDS Program, Beijing 100600, China.

^|| Current address: Centers for Disease Control, Central Business District, Abuja, FCT, Nigeria.

^¶ Current address: National Agency for Control of AIDS, Plot 823 Ralph Sodeinde Street, Central Business District, Abuja, FCT, Nigeria.

Show full affiliation list Hide full affiliation list

Viruses 2010, 2(1), 73-77; https://doi.org/10.3390/v2010073 - 11 Jan 2010

Cited by 2 | Viewed by 11309

Abstract

The national HIV seroprevalence in Nigeria has risen steeply from about 3% in 1993 to 5-8% in 2001 and now stands at 4.4%. HIV epidemic continues to be a serious threat to the most populous country in Africa with a population of 140 [...] Read more.

The national HIV seroprevalence in Nigeria has risen steeply from about 3% in 1993 to 5-8% in 2001 and now stands at 4.4%. HIV epidemic continues to be a serious threat to the most populous country in Africa with a population of 140 million, with limited use of antiviral drugs that is taken for life since it only suppresses the virus without completely eliminating the virus or leading to cure. Only a change in social behavior and an affordable vaccine can halt the epidemic in Africa. We report here results of a pilot study on the recruitment strategies, sociodemographic aspects and HIV risk behavior of a cohort of normal volunteers recruited at the University of Jos, Nigeria. Our study recorded a high degree of interest and zeal to participate in HIV vaccine studies by volunteers, and demonstrated the superiority of snowballing over invitation by mail, as a recruitment strategy. A cohort of university students may be particularly suitable for conducting HIV vaccine trials because of the assurance of prospective follow-up for up to four years (time to graduation), and a good understanding of the risks and benefits of participation as outlined in the informed consent. We had 100% retention during a follow-up period of two years. Most importantly, the cohort reflected a relatively low HIV seroprevalence, which gives preventive programs the potential to blunt or halt the epidemic. Full article

(This article belongs to the Special Issue AIDS Vaccine)

Review

Jump to: Research, Other

26 pages, 485 KiB

Open AccessReview

Applying Genomic and Bioinformatic Resources to Human Adenovirus Genomes for Use in Vaccine Development and for Applications in Vector Development for Gene Delivery

by Jason Seto¹, Michael P. Walsh¹, Padmanabhan Mahadevan², Qiwei Zhang³ and Donald Seto^1,*

¹ Department of Bioinformatics and Computational Biology, George Mason University, 10900 University Blvd., MSN 5B3, Manassas, VA 20110, USA

² Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA

³ Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong SAR, China

Viruses 2010, 2(1), 1-26; https://doi.org/10.3390/v2010001 - 6 Jan 2010

Cited by 16 | Viewed by 13970

Abstract

Technological advances and increasingly cost-effect methodologies in DNA sequencing and computational analysis are providing genome and proteome data for human adenovirus research. Applying these tools, data and derived knowledge to the development of vaccines against these pathogens will provide effective prophylactics. The same [...] Read more.

Technological advances and increasingly cost-effect methodologies in DNA sequencing and computational analysis are providing genome and proteome data for human adenovirus research. Applying these tools, data and derived knowledge to the development of vaccines against these pathogens will provide effective prophylactics. The same data and approaches can be applied to vector development for gene delivery in gene therapy and vaccine delivery protocols. Examination of several field strain genomes and their analyses provide examples of data that are available using these approaches. An example of the development of HAdV-B3 both as a vaccine and also as a vector is presented. Full article

(This article belongs to the Special Issue Novel Viral Vector Systems for Gene Therapy)

▼ Show Figures

Figure 1

18 pages, 3182 KiB

Open AccessReview

The IKK Kinases: Operators of Antiviral Signaling

by Alissa M. Pham¹ and Benjamin R. TenOever^1,2,*

¹ Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA

² Global Health and Emerging Pathogens Institute, New York, NY 10029, USA

Viruses 2010, 2(1), 55-72; https://doi.org/10.3390/v2010055 - 8 Jan 2010

Cited by 24 | Viewed by 13875

Abstract

The ability of a cell to combat an intracellular pathogen requires a mechanism to recognize the threat and elicit a transcriptional response against it. In the context of virus infection, the cell must take measures to inhibit viral replication, meanwhile, convey warning signals [...] Read more.

The ability of a cell to combat an intracellular pathogen requires a mechanism to recognize the threat and elicit a transcriptional response against it. In the context of virus infection, the cell must take measures to inhibit viral replication, meanwhile, convey warning signals to neighboring cells of the imminent threat. This immune response is predominantly mediated by the production of cytokines, notably, interferon beta (IFNβ). IFNβ signaling results in the transcriptional induction of over one hundred antiviral gene products whose timely expression renders infected cells more capable of inhibiting virus replication, while providing the uninfected cells with the reinforcements to generate a less permissive cellular environment. Induction of IFNβ and many aspects of the antiviral response pivot on the function of the IKK and IKK-related kinases. Despite sharing high levels of homology and some degree of functional redundancy, the classic IKK kinases: IKKα and IKKβ, and the IKK-related kinases: TBK1 and IKKε, perform distinct roles in regulating the host antiviral defense. These kinases serve as molecular operators in their cooperative ability to integrate incoming cellular cues and act on a range of essential antiviral transcription factors to reshape the cellular transcriptome during infection. Full article

(This article belongs to the Special Issue Interferon Antiviral Response and Viral Evasion)

▼ Show Figures

Figure 1

29 pages, 351 KiB

Open AccessReview

Oncolytic Viruses for Cancer Therapy: Overcoming the Obstacles

by Han Hsi Wong¹, Nicholas R. Lemoine^1,2 and Yaohe Wang^1,2,*

¹ Centre for Molecular Oncology and Imaging, Institute of Cancer, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK

² Sino-British Research Centre for Molecular Oncology, Zhengzhou University, Zhengzhou 450052, China

Viruses 2010, 2(1), 78-106; https://doi.org/10.3390/v2010078 - 11 Jan 2010

Cited by 144 | Viewed by 29189

Abstract

Targeted therapy of cancer using oncolytic viruses has generated much interest over the past few years in the light of the limited efficacy and side effects of standard cancer therapeutics for advanced disease. In 2006, the world witnessed the first government-approved oncolytic virus [...] Read more.

Targeted therapy of cancer using oncolytic viruses has generated much interest over the past few years in the light of the limited efficacy and side effects of standard cancer therapeutics for advanced disease. In 2006, the world witnessed the first government-approved oncolytic virus for the treatment of head and neck cancer. It has been known for many years that viruses have the ability to replicate in and lyse cancer cells. Although encouraging results have been demonstrated in vitro and in animal models, most oncolytic viruses have failed to impress in the clinical setting. The explanation is multifactorial, determined by the complex interactions between the tumor and its microenvironment, the virus, and the host immune response. This review focuses on discussion of the obstacles that oncolytic virotherapy faces and recent advances made to overcome them, with particular reference to adenoviruses. Full article

(This article belongs to the Special Issue Novel Viral Vector Systems for Gene Therapy)

▼ Show Figures

Figure 1

20 pages, 194 KiB

Open AccessReview

Retroviral Integration Site Selection

by Sébastien Desfarges and Angela Ciuffi^*

Institute of Microbiology, University Hospital Center and University of Lausanne, Bugnon 48, CH-1011 Lausanne, Switzerland

Viruses 2010, 2(1), 111-130; https://doi.org/10.3390/v2010111 - 12 Jan 2010

Cited by 57 | Viewed by 18492

Abstract

The stable insertion of a copy of their genome into the host cell genome is an essential step of the life cycle of retroviruses. The site of viral DNA integration, mediated by the viral-encoded integrase enzyme, has important consequences for both the virus [...] Read more.

The stable insertion of a copy of their genome into the host cell genome is an essential step of the life cycle of retroviruses. The site of viral DNA integration, mediated by the viral-encoded integrase enzyme, has important consequences for both the virus and the host cell. The analysis of retroviral integration site distribution was facilitated by the availability of the human genome sequence, revealing the non-random feature of integration site selection and identifying different favored and disfavored genomic locations for individual retroviruses. This review will summarize the current knowledge about retroviral differences in their integration site preferences as well as the mechanisms involved in this process. Full article

(This article belongs to the Special Issue Retroviral Enzymes)

▼ Show Figures

Graphical abstract

16 pages, 530 KiB

Open AccessReview

RNA Editing and its Control in Hepatitis Delta Virus Replication

by Renxiang Chen, Sarah D. Linnstaedt and John L. Casey^*

Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC 20007, USA

Viruses 2010, 2(1), 131-146; https://doi.org/10.3390/v2010131 - 12 Jan 2010

Cited by 11 | Viewed by 13581

Abstract

The hepatitis delta virus genome is a small circular RNA, similar to viroids. Although HDV contains a gene, the protein produced (HDAg) is encoded by less than half the genome and possesses no RNA polymerase activity. Because of this limited coding capacity, HDV [...] Read more.

The hepatitis delta virus genome is a small circular RNA, similar to viroids. Although HDV contains a gene, the protein produced (HDAg) is encoded by less than half the genome and possesses no RNA polymerase activity. Because of this limited coding capacity, HDV relies heavily on host functions and on structural features of the viral RNA—very much like viroids. The virus’ use of host RNA editing activity to produce two functionally distinct forms of HDAg is a particularly good example of this reliance. This review covers the mechanisms and control of RNA editing in the HDV replication cycle. Full article

(This article belongs to the Special Issue Subviral RNAs)

▼ Show Figures

Figure 1

19 pages, 1020 KiB

Open AccessReview

Comparative Studies on Retroviral Proteases: Substrate Specificity

by József Tözsér

Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, Egyetem tér 1, Debrecen, Hungary

Viruses 2010, 2(1), 147-165; https://doi.org/10.3390/v2010147 - 14 Jan 2010

Cited by 37 | Viewed by 15349

Abstract

Exogenous retroviruses are subclassified into seven genera and include viruses that cause diseases in humans. The viral Gag and Gag-Pro-Pol polyproteins are processed by the retroviral protease in the last stage of replication and inhibitors of the HIV-1 protease are widely used in [...] Read more.

Exogenous retroviruses are subclassified into seven genera and include viruses that cause diseases in humans. The viral Gag and Gag-Pro-Pol polyproteins are processed by the retroviral protease in the last stage of replication and inhibitors of the HIV-1 protease are widely used in AIDS therapy. Resistant mutations occur in response to the drug therapy introducing residues that are frequently found in the equivalent position of other retroviral proteases. Therefore, besides helping to understand the general and specific features of these enzymes, comparative studies of retroviral proteases may help to understand the mutational capacity of the HIV-1 protease. Full article

(This article belongs to the Special Issue Retroviral Enzymes)

▼ Show Figures

Graphical abstract

23 pages, 179 KiB

Open AccessReview

Targets for the Induction of Protective Immunity Against Influenza A Viruses

by Rogier Bodewes, Albert D.M.E. Osterhaus and Guus F. Rimmelzwaan^*

Department of Virology, ErasmusMC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands

Viruses 2010, 2(1), 166-188; https://doi.org/10.3390/v2010166 - 14 Jan 2010

Cited by 11 | Viewed by 12826

Abstract

The current pandemic caused by the new influenza A(H1N1) virus of swine origin and the current pandemic threat caused by the highly pathogenic avian influenza A viruses of the H5N1 subtype have renewed the interest in the development of vaccines that can induce [...] Read more.

The current pandemic caused by the new influenza A(H1N1) virus of swine origin and the current pandemic threat caused by the highly pathogenic avian influenza A viruses of the H5N1 subtype have renewed the interest in the development of vaccines that can induce broad protective immunity. Preferably, vaccines not only provide protection against the homologous strains, but also against heterologous strains, even of another subtype. Here we describe viral targets and the arms of the immune response involved in protection against influenza virus infections such as antibodies directed against the hemagglutinin, neuraminidase and the M2 protein and cellular immune responses directed against the internal viral proteins. Full article

(This article belongs to the Special Issue Influenza: Pandemics and Vaccinations)

▼ Show Figures

Graphical abstract

24 pages, 224 KiB

Open AccessReview

Interaction of Host Cellular Proteins with Components of the Hepatitis Delta Virus

by Valerie Greco-Stewart^1,2 and Martin Pelchat^1,*

¹ Department of Biochemistry, Microbiology & Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada

² Canadian Blood Services, 1800 Alta Vista Drive, Ottawa, Ontario, K1G 4J5, Canada

Viruses 2010, 2(1), 189-212; https://doi.org/10.3390/v2010189 - 18 Jan 2010

Cited by 42 | Viewed by 14962

Abstract

The hepatitis delta virus (HDV) is the smallest known RNA pathogen capable of propagation in the human host and causes substantial global morbidity and mortality. Due to its small size and limited protein coding capacity, HDV is exquisitely reliant upon host cellular proteins [...] Read more.

The hepatitis delta virus (HDV) is the smallest known RNA pathogen capable of propagation in the human host and causes substantial global morbidity and mortality. Due to its small size and limited protein coding capacity, HDV is exquisitely reliant upon host cellular proteins to facilitate its transcription and replication. Remarkably, HDV does not encode an RNA-dependent RNA polymerase which is traditionally required to catalyze RNA-templated RNA synthesis. Furthermore, HDV lacks enzymes responsible for post-transcriptional and -translational modification, processes which are integral to the HDV life cycle. This review summarizes the known HDV-interacting proteins and discusses their significance in HDV biology. Full article

(This article belongs to the Special Issue Subviral RNAs)

▼ Show Figures

Figure 1

31 pages, 623 KiB

Open AccessReview

Initiation of HIV Reverse Transcription

by Catherine Isel^*, Chantal Ehresmann and Roland Marquet^*

Architecture et Réactivité de l’ARN, Université de Strasbourg, CNRS, IBMC, 15 Rue René Descartes, 67084 Strasbourg cedex, France

Viruses 2010, 2(1), 213-243; https://doi.org/10.3390/v2010213 - 18 Jan 2010

Cited by 40 | Viewed by 16451

Abstract

Reverse transcription of retroviral genomes into double stranded DNA is a key event for viral replication. The very first stage of HIV reverse transcription, the initiation step, involves viral and cellular partners that are selectively packaged into the viral particle, leading to an [...] Read more.

Reverse transcription of retroviral genomes into double stranded DNA is a key event for viral replication. The very first stage of HIV reverse transcription, the initiation step, involves viral and cellular partners that are selectively packaged into the viral particle, leading to an RNA/protein complex with very specific structural and functional features, some of which being, in the case of HIV-1, linked to particular isolates. Recent understanding of the tight spatio-temporal regulation of reverse transcription and its importance for viral infectivity further points toward reverse transcription and potentially its initiation step as an important drug target. Full article

(This article belongs to the Special Issue Retroviral Enzymes)

▼ Show Figures

Figure 1

18 pages, 130 KiB

Open AccessReview

Virus Infection Recognition and Early Innate Responses to Non-Enveloped Viral Vectors

by Dmitry M. Shayakhmetov

Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195-7720, USA

Viruses 2010, 2(1), 244-261; https://doi.org/10.3390/v2010244 - 19 Jan 2010

Cited by 9 | Viewed by 12028

Abstract

Numerous human genetic and acquired diseases could be corrected or ameliorated if viruses are harnessed to safely and effectively deliver therapeutic genes to diseased cells and tissues in vivo. Innate immune and inflammatory response represents one of the key stumbling blocks during [...] Read more.

Numerous human genetic and acquired diseases could be corrected or ameliorated if viruses are harnessed to safely and effectively deliver therapeutic genes to diseased cells and tissues in vivo. Innate immune and inflammatory response represents one of the key stumbling blocks during the development of viral-based therapies. In this review, current data on the early innate immune responses to viruses and to the most commonly used gene therapy vectors (using adenovirus and adeno-associated virus) will be discussed. Recent findings in the field may help develop new approaches to moderate these innate immune anti-viral responses and thus improve the safety of viral vectors for human gene therapy applications. Full article

(This article belongs to the Special Issue Novel Viral Vector Systems for Gene Therapy)

▼ Show Figures

Figure 1

21 pages, 352 KiB

Open AccessReview

Evasion of the Interferon-Mediated Antiviral Response by Filoviruses

by Washington B. Cárdenas

Laboratorio de Biomedicina, FIMCM, Escuela Superior Politécnica del Litoral (ESPOL), Campus Gustavo Galindo, Km 30.5 via Perimetral, Apartado 09-01-5863, Guayaquil, Ecuador

Viruses 2010, 2(1), 262-282; https://doi.org/10.3390/v2010262 - 21 Jan 2010

Cited by 9 | Viewed by 15426

Abstract

The members of the filoviruses are recognized as some of the most lethal viruses affecting human and non-human primates. The only two genera of the Filoviridae family, Marburg virus (MARV) and Ebola virus (EBOV), comprise the main etiologic agents of severe hemorrhagic fever [...] Read more.

The members of the filoviruses are recognized as some of the most lethal viruses affecting human and non-human primates. The only two genera of the Filoviridae family, Marburg virus (MARV) and Ebola virus (EBOV), comprise the main etiologic agents of severe hemorrhagic fever outbreaks in central Africa, with case fatality rates ranging from 25 to 90%. Fatal outcomes have been associated with a late and dysregulated immune response to infection, very likely due to the virus targeting key host immune cells, such as macrophages and dendritic cells (DCs) that are necessary to mediate effective innate and adaptive immune responses. Despite major progress in the development of vaccine candidates for filovirus infections, a licensed vaccine or therapy for human use is still not available. During the last ten years, important progress has been made in understanding the molecular mechanisms of filovirus pathogenesis. Several lines of evidence implicate the impairment of the host interferon (IFN) antiviral innate immune response by MARV or EBOV as an important determinant of virulence. In vitro and in vivo experimental infections with recombinant Zaire Ebola virus (ZEBOV), the best characterized filovirus, demonstrated that the viral protein VP35 plays a key role in inhibiting the production of IFN-α/β. Further, the action of VP35 is synergized by the inhibition of cellular responses to IFN-α/β by the minor matrix viral protein VP24. The dual action of these viral proteins may contribute to an efficient initial virus replication and dissemination in the host. Noticeably, the analogous function of these viral proteins in MARV has not been reported. Because the IFN response is a major component of the innate immune response to virus infection, this chapter reviews recent findings on the molecular mechanisms of IFN-mediated antiviral evasion by filovirus infection. Full article

(This article belongs to the Special Issue Interferon Antiviral Response and Viral Evasion)

▼ Show Figures

Graphical abstract

15 pages, 107 KiB

Open AccessReview

The Development of an AIDS Mucosal Vaccine

by Xian Tang¹ and Zhiwei Chen^1,2,*

¹ AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

² Department of Microbiology and Research Center of Infection and Immunology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

Viruses 2010, 2(1), 283-297; https://doi.org/10.3390/v2010283 - 22 Jan 2010

Cited by 5 | Viewed by 12412

Abstract

It is well known that mucosal tissues contain the largest surface area of the human body and are the front line of natural host defense against various pathogens. In fact, more than 80% of infectious disease pathogens probably gain entry into the susceptible [...] Read more.

It is well known that mucosal tissues contain the largest surface area of the human body and are the front line of natural host defense against various pathogens. In fact, more than 80% of infectious disease pathogens probably gain entry into the susceptible human hosts through open mucosal surfaces. Human immunodeficiency virus type one (HIV-1), a mainly sexually transmitted virus, also primarily targets the vaginal and gastrointestinal mucosa as entry sites for viral transmission, seeding, replication and amplification. Since HIV-1 establishes its early replication in vaginal or rectal mucosal tissues, the induction of sufficient mucosal immunity at the initial site of HIV-1 transmission becomes essential for a protective vaccine. However, despite the fact that current conventional vaccine strategies have remained unsuccessful in preventing HIV-1 infection, sufficient financial support and resources have yet to be given to develop a vaccine able to elicit protective mucosal immunity against sexual transmissions. Interestingly, Chinese ancestors invented variolation through intranasal administration about one thousand years ago, which led to the discovery of a successful smallpox vaccine and the final eradication of the disease. It is the hope for all mankind that the development of a mucosal AIDS vaccine will ultimately help control the AIDS pandemic. In order to discover an effective mucosal AIDS vaccine, it is necessary to have a deep understanding of mucosal immunology and to test various mucosal vaccination strategies. Full article

(This article belongs to the Special Issue AIDS Vaccine)

16 pages, 148 KiB

Open AccessReview

Dual Role of p53 in Innate Antiviral Immunity

by Carmen Rivas¹, Stuart A. Aaronson² and Cesar Munoz-Fontela^2,*

¹ Centro Nacional de Biotecnologia, CSIC, Darwin 3, Campus Universidad Autónoma, Madrid 28049, Spain

² Department of Oncological Sciences, Mount Sinai School of Medicine, One Gustave L. Levy Place Box 1130, New York, NY 10029, USA

Viruses 2010, 2(1), 298-313; https://doi.org/10.3390/v2010298 - 22 Jan 2010

Cited by 107 | Viewed by 18000

Abstract

Tumor suppressor p53 is widely known as ‘the guardian of the genome’ due to its ability to prevent the emergence of transformed cells by the induction of cell cycle arrest and apoptosis. However, recent studies indicate that p53 is also a direct transcriptional [...] Read more.

Tumor suppressor p53 is widely known as ‘the guardian of the genome’ due to its ability to prevent the emergence of transformed cells by the induction of cell cycle arrest and apoptosis. However, recent studies indicate that p53 is also a direct transcriptional target of type I interferons (IFNs) and thus, it is activated by these cytokines upon viral infection. p53 has been shown to contribute to virus-induced apoptosis, therefore dampening the ability of a wide range of viruses to replicate and spread. Interestingly, recent studies also indicate that several IFN-inducible genes such as interferon regulatory factor 9 (IRF9), IRF5, IFN-stimulated gene 15 (ISG15) and toll-like receptor 3 (TLR3) are in fact, p53 direct transcriptional targets. These findings indicate that p53 may play a key role in antiviral innate immunity by both inducing apoptosis in response to viral infection, and enforcing the type I IFN response, and provide a new insight into the evolutionary reasons why many viruses encode p53 antagonistic proteins. Full article

(This article belongs to the Special Issue Interferon Antiviral Response and Viral Evasion)

▼ Show Figures

Graphical abstract

20 pages, 1056 KiB

Open AccessReview

Herpesviruses and Autophagy: Catch Me If You Can!

by Yolaine Cavignac and Audrey Esclatine^*

INSERM U756 and Université Paris-Sud 11, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément 92290 Châtenay-Malabry, France

Viruses 2010, 2(1), 314-333; https://doi.org/10.3390/v2010314 - 26 Jan 2010

Cited by 55 | Viewed by 16162

Abstract

Autophagy is an evolutionarily conserved cellular degradation pathway involving the digestion of intracellular components via the lysosomal pathway. The autophagic pathway constitutively maintains cellular homeostasis by recycling cytoplasmic organelles and proteins, but it is also stimulated by environmental stress conditions, such as starvation, [...] Read more.

Autophagy is an evolutionarily conserved cellular degradation pathway involving the digestion of intracellular components via the lysosomal pathway. The autophagic pathway constitutively maintains cellular homeostasis by recycling cytoplasmic organelles and proteins, but it is also stimulated by environmental stress conditions, such as starvation, oxidative stress, and the accumulation of misfolded proteins. It also acts as a cellular defense mechanism against microorganisms by contributing to both the innate and adaptive immunity, and by eliminating intracellular pathogens (xenophagy). There is growing evidence that host cells try to control Herpesvirus infections by activating the autophagic machinery. However, it is well-known that Herpesviruses are smart pathogens and several, such as HSV-1, HCMV and HHV-8, are known to have developed numerous defense strategies for evading the host’s immune response. Inhibition of the antiviral autophagic mechanism has also been reported. Autophagy has also been shown to enhance the major histocompatibility complex presentation of at least two viral proteins, the EBVencoded EBNA-1 and the HSV-1 encoded gB. In this review, we present an overview of recent advances in our understanding of the complex interplay between autophagy and Herpesviruses. Full article

(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)

▼ Show Figures

Figure 1

Other

Jump to: Research, Review

6 pages, 201 KiB

Open AccessCommentary

Nucleoproteins of Negative Strand RNA Viruses; RNA Binding, Oligomerisation and Binding to Polymerase Co-Factor

by Rob W. H. Ruigrok^* and Thibaut Crépin

Unit for Virus Host Cell Interactions, UMI 3265 UJF-EMBL-CNRS, BP 181, Grenoble cedex 9, France

Viruses 2010, 2(1), 27-32; https://doi.org/10.3390/v2010027 - 7 Jan 2010

Cited by 20 | Viewed by 10712

Abstract

Commentary on Tawar, R.G.; Duquerroy, S.; Vonrhein, C.; Varela, P.F.; Damier-Piolle, L.; Castagné, N.; MacLellan, K.; Bedouelle, H.; Bricogne, G.; Bhella, D.; Eléouët, J.-F.; Rey, F.A. Crystal structure of a nucleocapsid-like nucleoprotein-RNA complex of respiratory syncytial virus. Science 2009, 326, 1279-1283. Full article

▼ Show Figures

Figure 1

4 pages, 248 KiB

Open AccessCommentary

Correlative Structural Biology: How to Investigate the Fine Details of Viral Structure

by Elizabeth R. Wright

Emory University School of Medicine, Department of Pediatrics, Division of Pediatric Infectious Diseases, 2015 Uppergate Drive, NE, Atlanta, GA 30322, USA

Viruses 2010, 2(1), 107-110; https://doi.org/10.3390/v2010107 - 11 Jan 2010

Cited by 1 | Viewed by 9174

Abstract

Commentary on Byeon, I.J.; Meng, X.; Jung, J.; Zhao, G.; Yang, R.; Ahn, J.; Shi, J.; Concel, J.; Aiken, C.; Zhang, P.; Gronenborn, A.M. Structural convergence between Cryo-EM and NMR reveals intersubunit interactions critical for HIV-1 capsid function. Cell 2009, 139, 780-790. Full article

▼ Show Figures

Figure 1

Journal Menu

Journal Browser

Viruses, Volume 2, Issue 1 (January 2010) – 18 articles , Pages 1-333

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI