For best viewing of the website please use Mozilla Firefox or Google Chrome.
Serving the Society Since 1986
Articles in press have been peer-reviewed and accepted, which are not yet assigned to volumes/issues, but are citable by Digital Object Identifier (DOI).
Genome Characteristics and Evolution of Pseudorabies Virus Strains in Eastern China from 2017 to 2019
Xiaofeng Zhai, Wen Zhao, Kemang Li, Cheng Zhang, Congcong Wang, Shuo Su, Jiyong Zhou, Jing Lei, Gang Xing, Haifeng Sun, Zhiyu Shi, Jinyan Gu
doi: 10.1007/s12250-019-00140-1
Abstract PDF Springerlink ESM
Since late 2011, outbreaks of pseudorabies virus (PRV) have occurred in southern China causing major economic losses to the pig industry. We previously reported variant PRV may from recombination in China that could be the source of continued epidemics. Here, we analyzed samples from intensive pig farms in eastern China between 2017 and 2019, and sequenced the main glycoproteins (gB, gC, gD, and gE) to study the evolution characteristics of PRV. Based on the gC gene, we found that PRV variants belong to clade 2 and identified a founder effect by the PRV epidemic process. In addition, we detected inter- and intra-clade recombination, in particular, inter-clade recombination in the gB gene of strains FJ-ZXF and FJ-W2, which were recombinants with clade 1 strains. Specific amino acid changes and positively selected sites possibly associated with functional changes were also observed. The characteristics of PRV emergence in China necessitate continuous monitoring and development of vaccines capable of providing immunity against specific PRV variants.
Cleavage of the Babuvirus Movement Protein B4 into Functional Peptides Capable of Host Factor Conjugation is Required for Virulence
Jun Zhuang, Wenwu Lin, Christopher J. Coates, Pengxiang Shang, Taiyun Wei, Zujian Wu, Lianhui Xie
doi: 10.1007/s12250-019-00094-4
Abstract PDF Springerlink ESM
Banana bunchy top virus (BBTV) poses a serious danger to banana crops worldwide. BBTV-encoded protein B4 is a determinant of pathogenicity. However, the relevant molecular mechanisms underlying its effects remain unknown. In this study, we found that a functional peptide could be liberated from protein B4, likely via proteolytic processing. Site-directed mutagenesis indicated that the functional processing of protein B4 is required for its pathogenic effects, including dwarfism and sterility, in plants. The released protein fragment targets host proteins, such as the large subunit of RuBisCO (RbcL) and elongation factor 2 (EF2), involved in protein synthesis. Therefore, the peptide released from B4 (also a precursor) may act as a non-canonical modifier to influence host–pathogen interactions involving BBTV and plants.
Rift Valley Fever Virus and Yellow Fever Virus in Urine: A Potential Source of Infection
Meng Li, Beibei Wang, Liqiang Li, Gary Wong, Yingxia Liu, Jinmin Ma, Jiandong Li, Hongzhou Lu, Mifang Liang, Ang Li, Xiuqing Zhang, Yuhai Bi, Hui Zeng
doi: 10.1007/s12250-019-00096-2
Abstract PDF Springerlink ESM
In recent years, the incidence of human infections caused by emerging or re-emerging pathogens has rapidly increased. Diseases that were once regional now have the ability to spread globally in a short amount of time and pose a wider threat to public health (Weaver et al. 2018). Yellow fever virus (YFV, family Flaviviridae, genus Flavivirus) is a mosquito-borne flavivirus that causes yellow fever in humans and has been endemic in Africa and Latin America for many years (Domingo et al. 2018). The most recent large-scale outbreak of YFV occurred in Brazil in which the mortality rate as of February 28, 2018 is 32.78% (WHO 2018). Rift Valley fever virus (RVFV, family Bunyaviridae, genus Phlebovirus) is another mosquitoborne virus and primarily circulates in Africa and the Middle East, and in recent years in Europe (Mansfield et al. 2015). During the initial stage of infection, most patients infected with YFV or RVFV present nonspecific symptoms such as fever, headache, and vomiting, which often lead to a misdiagnosis (Mansfield et al. 2015; Domingo et al. 2018). The cases of YFV and RVFV in China were first reported in March and July 2016, respectively, in travelers returning from Angola (Chen et al. 2016; Liu et al. 2017).
Bacteriophages Isolated in China for the Control of Pectobacterium carotovorum Causing Potato Soft Rot in Kenya
Peter Muturi, Junping Yu, Alice Nyambura Maina, Samuel Kariuki, Francis B. Mwaura, Hongping Wei
doi: 10.1007/s12250-019-00091-7
Abstract PDF Springerlink ESM
Soft rot is an economically significant disease in potato and one of the major threats to sustainable potato production. This study aimed at isolating lytic bacteriophages and evaluating methods for and the efficacy of applying phages to control potato soft rot caused by Pectobacterium carotovorum. Eleven bacteriophages isolated from soil and water samples collected in Wuhan, China, were used to infect P. carotovorum host strains isolated from potato tubers showing soft rot symptoms in Nakuru county, Kenya. The efficacy of the phages in controlling soft rot disease was evaluated by applying individual phage strains or a phage cocktail on potato slices and tubers at different time points before or after inoculation with a P. carotovorum strain. The phages could lyse 20 strains of P. carotovorum, but not Pseudomonas fluorescenscontrol strains. Among the 11 phages, Pectobacterium phage Wc5r, interestingly showed cross-activity against Pectobacterium atrosepticum and two phage-resistant P. carotovorum strains. Potato slice assays showed that the phage concentration and timing of application are crucial factors for effective soft rot control. Phage cocktail applied at a concentration of 1 × 109 plaque-forming units per milliliter before or within an hour after bacterial inoculation on potato slices, resulted in ≥90% reduction of soft rot symptoms. This study provides a basis for the development and application of phages to reduce the impact of potato soft rot disease.

|     

Preface
Preface
Zhi-Ming Zheng, Ke Lan, Eric O. Freed, Zheng-Li Shi
2019, 34(2): 117-118.  doi: 10.1007/s12250-019-00118-z
HTML Full Text [PDF 357KB] Springerlink
Review
Multiple Roles of HIV-1 Capsid during the Virus Replication Cycle
Mariia Novikova, Yulan Zhang, Eric O. Freed, Ke Peng
2019, 34(2): 119-134.  doi: 10.1007/s12250-019-00095-3
HTML Full Text [PDF 1752KB] Springerlink
Human immunodeficiency virus-1 capsid (HIV-1 CA) is involved in different stages of the viral replication cycle. During virion assembly, CA drives the formation of the hexameric lattice in immature viral particles, while in mature virions CA monomers assemble in cone-shaped cores surrounding the viral RNA genome and associated proteins. In addition to its functions in late stages of the viral replication cycle, CA plays key roles in a number of processes during early phases of HIV-1 infection including trafficking, uncoating, recognition by host cellular proteins and nuclear import of the viral preintegration complex. As a result of efficient cooperation of CA with other viral and cellular proteins, integration of the viral genetic material into the host genome, which is an essential step for productive viral infection, successfully occurs. In this review, we will summarize available data on CA functions in HIV-1 replication, describing in detail its roles in late and early phases of the viral replication cycle.
Towards Better Understanding of KSHV Life Cycle: from Transcription and Posttranscriptional Regulations to Pathogenesis
Lijun Yan, Vladimir Majerciak, Zhi-Ming Zheng, Ke Lan
2019, 34(2): 135-161.  doi: 10.1007/s12250-019-00114-3
HTML Full Text [PDF 1571KB] Springerlink
Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8 (HHV-8), is etiologically linked to the development of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. These malignancies often occur in immunosuppressed individuals, making KSHV infection-associated diseases an increasing global health concern with persistence of the AIDS epidemic. KSHV exhibits biphasic life cycles between latent and lytic infection and extensive transcriptional and posttranscriptional regulation of gene expression. As a member of the herpesvirus family, KSHV has evolved many strategies to evade the host immune response, which help the virus establish a successful lifelong infection. In this review, we summarize the current research status on the biology of latent and lytic viral infection, the regulation of viral life cycles and the related pathogenesis.
Flu DRiPs in MHC Class Ⅰ Immunosurveillance
Jiajie Wei, Jonathan W. Yewdell
2019, 34(2): 162-167.  doi: 10.1007/s12250-018-0061-y
HTML Full Text [PDF 390KB] Springerlink
Since the publication of the DRiP (defective ribosomal product) hypothesis in 1996, numerous studies have addressed the contribution of DRiPs to generating viral antigenic peptides for CD8+ T cell immunosurveillance. Here, we review studies characterizing the generation of antigenic peptides from influenza A virus encoded DRiPs, discuss the many remaining mysteries regarding the nature of their co-translational generation, and speculate on where the future might lead.
Development of Neutralizing Antibodies against Zika Virus Based on Its Envelope Protein Structure
Chunpeng Yang, Rui Gong, Natalia de Val
2019, 34(2): 168-174.  doi: 10.1007/s12250-019-00093-5
HTML Full Text [PDF 1223KB] Springerlink
As we know more about Zika virus (ZIKV), as well as its linkage to birth defects (microcephaly) and autoimmune neurological syndromes, we realize the importance of developing an efficient vaccine against it. Zika virus disease has affected many countries and is becoming a major public health concern. To deal with the infection of ZIKV, plenty of experiments have been done on selection of neutralizing antibodies that can target the envelope (E) protein on the surface of the virion. However, the existence of antibody-dependent enhancement (ADE) effect might limit the use of them as therapeutic candidates. In this review, we classify the neutralizing antibodies against ZIKV based on the epitopes and summarize the resolved structural information on antibody/antigen complex from X-ray crystallography and cryo-electron microscopy (cryo-EM), which might be useful for further development of potent neutralizing antibodies and vaccines toward clinical use.
Viral Regulation of RNA Granules in Infected Cells
Qiang Zhang, Nishi R. Sharma, Zhi-Ming Zheng, Mingzhou Chen
2019, 34(2): 175-191.  doi: 10.1007/s12250-019-00122-3
HTML Full Text [PDF 1155KB] Springerlink
RNA granules are cytoplasmic, microscopically visible, non-membrane ribo-nucleoprotein structures and are important posttranscriptional regulators in gene expression by controlling RNA translation and stability. TIA/G3BP/PABP-specific stress granules (SG) and GW182/DCP-specific RNA processing bodies (PB) are two major distinguishable RNA granules in somatic cells and contain various ribosomal subunits, translation factors, scaffold proteins, RNA-binding proteins, RNA decay enzymes and helicases to exclude mRNAs from the cellular active translational pool. Although SG formation is inducible due to cellular stress, PB exist physiologically in every cell. Both RNA granules are important components of the host antiviral defense. Virus infection imposes stress on host cells and thus induces SG formation. However, both RNA and DNA viruses must confront the hostile environment of host innate immunity and apply various strategies to block the formation of SG and PB for their effective infection and multiplication. This review summarizes the current research development in the field and the mechanisms of how individual viruses suppress the formation of host SG and PB for virus production.
Manipulating the Interferon Signaling Pathway: Implications for HIV Infection
Krystelle Nganou-Makamdop, Daniel C. Douek
2019, 34(2): 192-196.  doi: 10.1007/s12250-019-00085-5
HTML Full Text [PDF 387KB] Springerlink
During human immunodeficiency virus (HIV) infection, type Ⅰ interferon (IFN-Ⅰ) signaling induces an antiviral state that includes the production of restriction factors that inhibit virus replication, thereby limiting the infection. As seen in other viral infections, type Ⅰ IFN can also increase systemic immune activation which, in HIV disease, is one of the strongest predictors of disease progression to acquired immune deficiency syndrome (AIDS) and non-AIDS morbidity and mortality. Moreover, IFN-Ⅰ is associated with CD4 T cell depletion and attenuation of antigen-specific T cell responses. Therefore, therapeutic manipulation of IFN-Ⅰ signaling to improve HIV disease outcome is a source of much interest and debate in the field. Recent studies have highlighted the importance of timing (acute vs. chronic infection) and have suggested that specific targeting of type Ⅰ IFNs and their subtypes may help harness the beneficial roles of the IFN-Ⅰ system while avoiding its deleterious activities.
Research Article
MicroRNA-135a Modulates Hepatitis C Virus Genome Replication through Downregulation of Host Antiviral Factors
Catherine Sodrosk, Brianna Lowey, Laura Hertz, T. Jake Liang, Qisheng Li
2019, 34(2): 197-210.  doi: 10.1007/s12250-018-0055-9
HTML Full Text [PDF 3041KB] Springerlink ESM
Cellular microRNAs (miRNAs) have been shown to modulate HCV infection via directly acting on the viral genome or indirectly through targeting the virus-associated host factors. Recently we generated a comprehensive map of HCV– miRNA interactions through genome-wide miRNA functional screens and transcriptomics analyses. Many previously unappreciated cellular miRNAs were identified to be involved in HCV infection, including miR-135a, a human cancerrelated miRNA. In the present study, we investigated the role of miR-135a in regulating HCV life cycle and showed that it preferentially enhances viral genome replication. Bioinformatics-based integrative analyses and subsequent functional assays revealed three antiviral host factors, including receptor interacting serine/threonine kinase 2 (RIPK2), myeloid differentiation primary response 88 (MYD88), and C-X-C motif chemokine ligand 12 (CXCL12), as bona fide targets of miR-135a. These genes have been shown to inhibit HCV infection at the RNA replication stage. Our data demonstrated that repression of key host restriction factors mediated the proviral effect of miR-135a on HCV propagation. In addition, miR-135a hepatic abundance is upregulated by HCV infection in both cultured hepatocytes and human liver, likely mediating a more favorable environment for viral replication and possibly contributing to HCV-induced liver malignancy. These results provide novel insights into HCV–host interactions and unveil molecular pathways linking miRNA biology to HCV pathogenesis.
HPV18 Utilizes Two Alternative Branch Sites for E6*I Splicing to Produce E7 Protein
Ayslan Castro Brant, Vladimir Majerciak, Miguel Angelo Martins Moreira, Zhi-Ming Zheng
2019, 34(2): 211-221.  doi: 10.1007/s12250-019-00098-0
HTML Full Text [PDF 951KB] Springerlink ESM
Human papillomavirus 18 (HPV18) E6 and E7 oncogenes are transcribed as a single bicistronic E6E7 pre-mRNA. The E6 ORF region in the bicistronic E6E7 pre-mRNA contains an intron. Splicing of this intron disrupts the E6 ORF integrity and produces a spliced E6*I RNA for efficient E7 translation. Here we report that the E6 intron has two overlapped branch point sequences (BPS) upstream of its 3' splice site, with an identical heptamer AACUAAC, for E6*I splicing. One heptamer has a branch site adenosine (underlined) at nt 384 and the other at nt 388. E6*I splicing efficiency correlates to the expression level of E6 and E7 proteins and depends on the selection of which branch site. In general, E6*I splicing prefers the 3'ss-proximal branch site at nt 388 over the distal branch site at nt 384. Inactivation of the nt 388 branch site was found to activate a cryptic acceptor site at nt 636 for aberrant RNA splicing. Together, these data suggest that HPV18 modulates its production ratio of E6 and E7 proteins by alternative selection of the two mapped branch sites for the E6*I splicing, which could be beneficial in its productive or oncogenic infection according to the host cell environment.
Prion Protein Protects Cancer Cells against Endoplasmic Reticulum Stress Induced Apoptosis
Zhenxing Gao, Min Peng, Liang Chen, Xiaowen Yang, Huan Li, Run Shi, Guiru Wu, Lili Cai, Qibin Song, Chaoyang Li
2019, 34(2): 222-234.  doi: 10.1007/s12250-019-00107-2
HTML Full Text [PDF 6855KB] Springerlink ESM
Unfolded protein response (UPR) is an adaptive reaction for cells to reduce endoplasmic reticulum (ER) stress. In many types of cancers, such as lung cancer and pancreatic cancer, cancer cells may harness ER stress to facilitate their survival and growth. Prion protein (PrP) is a glycosylated cell surface protein that has been shown to be up-regulated in many cancer cells. Since PrP is a protein prone to misfolding, ER stress can result in under-glycosylated PrP, which in turn may activate ER stress. To assess whether ER stress leads to the production of under-glycosylated PrP and whether underglycosylated PrP may contribute to ER stress thus leading to cancer cell apoptosis, we treated different cancer cells with brefeldin A (BFA), thapsigargin (Thps), and tunicamycin (TM). We found that although BFA, Thps, and TM treatment activated UPR, only ATF4 was consistently activated by these reagents, but not other branches of ER stress. However, the canonical PERK-eIF2α-ATF4 did not account for the observed activation of ATF4 in lung cancer cells. In addition, BFA, but neither Thps nor TM, significantly stimulated the expression of cytosolic PrP. Finally, we found that the levels of PrP contributed to anti-apoptosis activity of BFA-induced cancer cell death. Thus, the pathway of BFA-induced persistent ER stress may be targeted for lung and pancreatic cancer treatment.