Rong Hai

University of California, Riverside

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Peter Palese

Icahn School of Medicine at Mount Sinai

Dongzheng Yu

Anhui University

Adolfo García‐Sastre

Icahn School of Medicine at Mount Sinai

Florian Krammer

Icahn School of Medicine at Mount Sinai

Enmin Zhang

National Institute for Communicable Disease Control and Prevention

Yu‐Fang Pei

Soochow University

Lei Zhang

Ministry of Agriculture and Rural Affairs

Zhikai Zhang

North Minzu University

Jianchun Wei

National Institute for Communicable Disease Control and Prevention

Hong‐Wen Deng

Tulane University

Cooperative Institutions

Icahn School of Medicine at Mount Sinai

National Institute for Communicable Disease Control and Prevention

Chinese Center For Disease Control and Prevention

Chinese Academy of Sciences

University of California, Riverside

Center for Disease Control

Chinese Academy of Medical Sciences & Peking Union Medical College

Soochow University

Peking University

Shanghai Jiao Tong University

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Chimeric Hemagglutinin Influenza Virus Vaccine Constructs Elicit Broadly Protective Stalk-Specific Antibodies

Journal of Virology (2013)

Florian Krammer Natalie Pica Rong Hai Irina Margine Peter Palese

ABSTRACT Current influenza virus vaccine strategies stimulate immune responses toward the globular head domain of the hemagglutinin protein in order to inhibit key steps of the virus life cycle. Because this domain is highly variable across strains, new vaccine formulations are required in most years. Here we demonstrate a novel vaccine strategy that generates immunity to the highly conserved stalk domain by using chimeric hemagglutinin constructs that express unique head and stalk combinations. By repeatedly immunizing mice with constructs that expressed the same stalk but an irrelevant head, we specifically stimulated a stalk-directed response that provided broad-based heterologous and heterosubtypic immunity in mice. Notably, our vaccination scheme provides a universal vaccine approach that protects against challenge with an H5 subtype virus. Furthermore, through in vivo studies using passively transferred antibodies or depletion of CD8 + T cells, we demonstrated the critical role that humoral mechanisms of immunity play in the protection observed. The present data suggest that a vaccine strategy based on the stalk domain of the hemagglutinin protein could be used in humans to broadly protect against a variety of influenza virus subtypes.

Heterologous

10.1128/jvi.00641-13

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Citations (394)

Genome Rearrangements of Completely Sequenced Strains of Yersinia pestis

Journal of Clinical Microbiology (2010)

Ying Liang Xuexin Hou Yanhua Wang Zhigang Cui Zhikai Zhang

Yersinia pestis has caused three worldwide plagues in human history that have led to innumerable deaths. We have completely sequenced the genomes of two strains (D106004 and D182038) of Y. pestis isolated from Yunnan Province of China. The most striking finding of our study is that large amounts of genome rearrangement events exist between the genomes of two Yunnan strains despite being isolated from two foci only 50 kilometers apart. When we compared the genome sequences of the Yunnan strains with six strains (CO92, KIM, 91001, Antiqua, Nepal516, and Pestoides F) of Y. pestis sequenced previously, we found that the genomes of Y. pestis were divided into 61 relatively independent segments. Pairwise comparisons of all 61 segments among eight strains showed that the Yunnan strains were most closely related to strain CO92. We concluded that Y. pestis genomes consist of segments that can change their positions and directions within the genomes caused by genome rearrangements, and our study confirmed the inference that the third plague pandemic originated in Yunnan since the genome sequences of Yunnan strains were closest to the strain CO92 isolated from the United States.

Yersinia pestis

plague

Strain (injury)

Comparative Genomics

10.1128/jcm.01473-09

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Citations (17)

Comparison of antigenic differences in the HA structures of 1918, Cal/09 and Bris/59/07 viruses.

Balaji Manicassamy A. Medina Rafael Rong Hai Tshidi Tsibane Silke Stertz

10.1371/journal.ppat.1000745.g006

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Citations (0)

Genome-wide association meta-analyses identified 1q43 and 2q32.2 for hip Ward's triangle areal bone mineral density

Bone (2016)

Yu‐Fang Pei Wen‐Zhu Hu Rong Hai Xiuyan Wang Shu Ran

Trochanter

Genome-wide Association Study

FRAX

10.1016/j.bone.2016.07.004

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Citations (12)

Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection

Immunity (2016)

Nicholas S. Heaton Natasha Moshkina Romain Fenouil Thomas J. Gardner Sebastián Aguirre

Proteostasis

Antibody-dependent enhancement

10.1016/j.immuni.2016.01.016

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Citations (1)

Involvement of the Skeletal Renin-Angiotensin System in Age-Related Osteoporosis of Ageing Mice

Bioscience Biotechnology and Biochemistry (2012)

Sa-Sa Gu Yan Zhang Xiaoli Li Shuyan Wu Teng‐Yue Diao

The local tissue-specific renin-angiotensin system (RAS) was identified. The aim of this study was to investigate the role of local bone RAS in the osteoporosis of aging mice. Twelve-month-old and two-month-old male mice were respectively assigned to the ageing and young groups. The tibias and femurs were collected for an analysis of histomorphology, bone mass, and gene and protein expression. H&E staining and micro-CT measurement showed a loss of the trabecular bone network and decrease of bone mineral density in the proximal tibial metaphysis of the aged mice. The PCR results indicated the significant up-regulation of renin and angiotensinogen (AGT) mRNA expression in both the tibia and femur of the ageing mice. Western blotting data showed that the tibial angiotensin II protein expression was significantly increased in the ageing group. The enhancement of renin and AGT expression in the bone tissue resulted in the increased production of angiotensin II which plays an important role in the pathology of age-related osteoporosis.

10.1271/bbb.120123

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Citations (55)

Naturally Occurring Human Monoclonal Antibodies Neutralize both 1918 and 2009 Pandemic Influenza A (H1N1) Viruses

Journal of Virology (2009)

Jens C. Krause Terrence M. Tumpey Chelsey J. Huffman Patricia McGraw Melissa B. Pearce

The 2009 pandemic influenza A (H1N1) virus exhibits hemagglutinin protein sequence homology with the 1918 pandemic influenza virus. We found that human monoclonal antibodies recognized the Sa antigenic site on the head domains of both 1918 and 2009 hemagglutinins, a site that is hypervariable due to immune selection. These antibodies exhibited high potency against the 2009 virus in vitro, and one exerted a marked therapeutic effect in vivo.

Pandemic

H5N1 genetic structure

Hypervariable region

10.1128/jvi.02184-09

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Citations (96)

Human antibodies targeting Zika virus NS1 provide protection against disease in a mouse model

Nature Communications (2018)

Mark Bailey James Duehr Harrison Dulin Felix Broecker Julia A. Brown

Abstract Zika virus is a mosquito-borne flavivirus closely related to dengue virus that can cause severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. Specific treatments and vaccines for Zika virus are not currently available. Here, we isolate and characterize four monoclonal antibodies (mAbs) from an infected patient that target the non-structural protein NS1. We show that while these antibodies are non-neutralizing, NS1-specific mAbs can engage FcγR without inducing antibody dependent enhancement (ADE) of infection in vitro. Moreover, we demonstrate that mAb AA12 has protective efficacy against lethal challenges of African and Asian lineage strains of Zika virus in Stat2 –/– mice. Protection is Fc-dependent, as a mutated antibody unable to activate known Fc effector functions or complement is not protective in vivo. This study highlights the importance of the ZIKV NS1 protein as a potential vaccine antigen.

Zika Virus

Flavivirus

Antibody-dependent enhancement

Vero cell

10.1038/s41467-018-07008-0

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Citations (95)

Locus-specific analysis of IS100 insertion within Yersinia pestis genome

Zhongguo difangbingxue zazhi (2008)

Lina Li Dongzheng Yu Rong Hai Jianchun Wei FU Xiu-ping

Objective To study the genotyping distribution of the Yersinia pestis(Y.pestis)strains by characterizing the diversity of the insertion sequence IS100 within the Y.pestis genome.Methods Derived fromthe known sequence of oriental strain CO92,5 pairs of locus-specific primers originating from both sides of the adjacent region of IS100 copies were designed,and two other complementary primers inside the IS100 sequence were designed to correspond with the outer primers.Then,91 Y.pestis strains and l pseudotubebculosis strain were tested by the specific PCR method using the primers described above and the PCR products were conformed by the sequence analysis,then further analysis WaS performed after the IS100 status was marked on the map of the plague focus type of china.Results The 91 Y.pestis strains had different IS100 status in their genome on tested loci.some possessed IS100 insertion,some didn't,and others changed their genome constitution.The IS100 possession on the 5 loci also suggested a distribution of regionality.Conclusion The analysis of some IS100 insertion element loci reveals that the IS100 genotyping distribution is consistent with the plague focus of type of China.And IS100genotyping pattern of the Y.pestis stains well reflects its genome constitution and the high flowability in its natural evolution. Key words: Yersiniapestis; Genome; DNA transposable elements

Yersinia pestis

Insertion sequence

10.3760/cma.j.issn.1000-4955.2008.06.004

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In Vitro and In Vivo Characterization of a Murine Cytomegalovirus with a Mutation at Open Reading Frame m166

Journal of Virology (2003)

Jiaming Zhu Jennifer Chen Rong Hai Tuong Tong Jianqiao Xiao

We have recently generated a pool of murine cytomegalovirus (MCMV) mutants by using a Tn3-based transposon mutagenesis approach. In this study, one of the mutants, Rvm166, which contained the transposon sequence at open reading frame m166, was characterized both in tissue culture and in immunocompetent BALB/c mice and immunodeficient SCID mice. The viral mutant replicated as well as the wild-type Smith strain in vitro in NIH 3T3 cells, whereas the transposon insertion precluded the expression of >65% of the m166 open reading frame. Compared to the wild-type strain and a rescued virus that restored the m166 region, the viral mutant was significantly attenuated in growth in both BALB/c and SCID mice that were intraperitoneally infected with the viruses. At 21 days postinfection, the titers of the viral mutant in the salivary glands, lungs, spleens, livers, and kidneys of the infected SCID mice were lower than the titers of the Smith strain and the rescued virus by about 30000-, 10000-, 1000-, 300-, and 800-fold, respectively. Moreover, the virulence of the mutant virus appears to be severely attenuated because no death was found in SCID mice infected with the viral mutant up to 90 days postinfection, whereas all of the animals infected with the wild-type and rescued viruses died at 27 days postinfection. Our results suggest that m166 probably encodes a virulence factor and is required for MCMV virulence in killing SCID mice and for optimal viral growth in vivo.

Serial passage

Transposon mutagenesis

10.1128/jvi.77.5.2882-2891.2003

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Citations (11)