Virology Commons^™

Species D Adenoviruses As Oncolytic Viral Vectors, Brianna L. Bullard, Brigette N. Corder, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Oncolytic adenoviruses (Ad) have shown promising results in the therapeutic treatment of cancer. Ad type 5 (Ad5) is the most extensively utilized Ad type. However, several limitations exist to using Ad5 as an oncolytic virus, including high levels of anti-Ad5 neutralizing antibodies in the population, binding of the Ad5 hexon to blood coagulation factor X leading to liver sequestration and toxicity, and reduced expression of the primary receptor CAR on many tumors. Here, we use in vitro methods to explore the oncolytic potential of four alternative Ad types (Ad26, 28, 45, and 48) belonging to the species D Ad subgroup …

Chloroviruses, James L. Van Etten, Irina V. Agarkova, David D. Dunigan

Nebraska Center for Virology: Faculty Publications

Chloroviruses are large dsDNA, plaque-forming viruses that infect certain chlorella-like green algae; the algae are normally mutualistic endosymbionts of protists and metazoans and are often referred to as zoochlorellae. The viruses are ubiquitous in inland aqueous environments throughout the world and occasionally single types reach titers of thousands of plaque-forming units per ml of native water. The viruses are icosahedral in shape with a spike structure located at one of the vertices. They contain an internal membrane that is required for infectivity. The viral genomes are 290 to 370 kb in size, which encode up to 16 tRNAs and 330 …

Genome-Wide Variation In Potyviruses, Deepti Nigam, Katherine Latourrette, Pedro F.N. Souza, Hernan Garcia Ruiz

Nebraska Center for Virology: Faculty Publications

Potyviruses (family Potyviridae, genus Potyvirus) are the result of an initial radiation event that occurred 6,600 years ago. The genus currently consists of 167 species that infect monocots or dicots, including domesticated and wild plants. Potyviruses are transmitted in a non-persistent way by more than 200 species of aphids. As indicated by their wide host range, worldwide distribution, and diversity of their vectors, potyviruses have an outstanding capacity to adapt to new hosts and environments. However, factors that confer adaptability are poorly understood. Viral RNA-dependent RNA polymerases introduce nucleotide substitutions that generate genetic diversity. We hypothesized that selection imposed by …

Macrophage-Associated Wound Healing Contributes To African Green Monkey Siv Pathogenesis Control, Fredrik Barrenas, Kevin Raehtz, Cuiling Xu, Lynn Law, Richard R. Green, Guido Silvestri, Steven E. Bosinger, Andrew Nishida, Qingsheng Li, Wuxun Lu, Jianshui Zhang, Matthew J. Thomas, Jean Chang, Elise Smith, Jeffrey M. Weiss, Reem A. Dawoud, George H. Richter, Anita Trichel, Dongzhu Ma, Xinxia Peng, Jan Komorowski, Cristian Apetrei, Ivona Pandrea, Michael Gale Jr.

Nebraska Center for Virology: Faculty Publications

Natural hosts of simian immunodeficiency virus (SIV) avoid AIDS despite lifelong infection. Here, we examined how this outcome is achieved by comparing a natural SIV host, African green monkey (AGM) to an AIDS susceptible species, rhesus macaque (RM). To asses gene expression profiles from acutely SIV infected AGMs and RMs, we developed a systems biology approach termed Conserved Gene Signature Analysis (CGSA), which compared RNA sequencing data from rectal AGM and RM tissues to various other species. We found that AGMs rapidly activate, and then maintain, evolutionarily conserved regenerative wound healing mechanisms in mucosal tissue. The wound healing protein fibronectin …

Dose Effects Of Recombinant Adenovirus Immunization In Rodents, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Recombinant adenovirus type 5 (rAd) has been used as a vaccine platform against many infectious diseases and has been shown to be an effective vaccine vector. The dose of the vaccine varies significantly from study to study, making it very diffcult to compare immune responses and vaccine effcacy. This study determined the immune correlates induced by serial dilutions of rAd vaccines delivered intramuscularly (IM) and intranasally (IN) to mice and rats. When immunized IM, mice had substantially higher antibody responses at the higher vaccine doses, whereas, the IN immunized mice showed a lower response to the higher rAd vaccine doses. …

The Vaccinia Virus (Vacv) B1 And Cellular Vrk2 Kinases Promote Vacv Replication Factory Formation Through Phosphorylation-Dependent Inhibition Of Vacv B12, Amber B. Rico, Zhigang Wang, Annabel T. Olson, Alexandria C. Linville, Brianna L. Bullard, Eric A. Weaver, Clinton Jones, Matthew S. Wiebea

Nebraska Center for Virology: Faculty Publications

Comparative examination of viral and host protein homologs reveals novel mechanisms governing downstream signaling effectors of both cellular and viral origin. The vaccinia virus B1 protein kinase is involved in promoting multiple facets of the virus life cycle and is a homolog of three conserved cellular enzymes called vaccinia virus-related kinases (VRKs). Recent evidence indicates that B1 and VRK2 mediate a common pathway that is largely uncharacterized but appears independent of previous VRK substrates. Interestingly, separate studies described a novel role for B1 in inhibiting vaccinia virus protein B12, which otherwise impedes an early event in the viral lifecycle. Herein, …

Rig-I-Like Receptors Direct Inflammatory Macrophage Polarization Against West Nile Virus Infection., Amy E. L. Stone, Richard Green, Courtney Wilkins, Emily A. Hemann, Michael Gale Jr.

College of Osteopathic Medicine (TUN) Publications and Research

RIG-I-Like Receptors (RLRs) RIG-I, MDA5, and LGP2, are vital pathogen recognition receptors in the defense against RNA viruses. West Nile Virus (WNV) infections continue to grow in the US. Here, we use a systems biology approach to define the contributions of each RLR in the innate immune response to WNV. Genome-wide RNAseq and bioinformatics analyses of macrophages from mice lacking either RLR reveal that the RLRs drive distinct immune gene activation and response polarization to mediate an M1/inflammatory signature while suppressing the M2/wound healing phenotype. While LGP2 functions to modulate inflammatory signaling, RIG-I and MDA5 together are essential for M1 …

Longitudinal Quantification Of Adenovirus Neutralizing Responses In Zambian Mother-Infant Pairs: Impact Of Hiv-1 Infection And Its Treatment, Sara R. Privatt, Brianna L. Bullard, Eric A. Weaver, Charles Wood, John T. West

Nebraska Center for Virology: Faculty Publications

Vaccination offers the most cost-effective approach to limiting the adverse impact of infectious and neoplastic diseases that reduce the quality of life in sub-Saharan Africa (SSA). However, it is unclear what vaccine vectors would be most readily implementable in the setting and at what age they should be applied for maximal efficacy. Adenoviruses (Ad) and Ad-based vectors have been demonstrated to induce effective humoral and cellular immune responses in animal models and in humans. However, because immunity associated with Ad infection is lifelong, there exists a debate as to whether pre-existing immunity might decrease the efficacy of Ad vectored vaccines. …

Role Of Gp120 Glycosylation In Sexual Transmission Of Hiv, Yingxue Sun, Adam Meadows, Najwa Zebian, Eric Arts, Carole Creuzenet

Western Research Forum

Background:

In chronic HIV patients, the viral populations are genetically diverse due to mutations introduced by the viral reverse transcriptase during HIV replication. However, more than 80% new infections result from single transmission founder (TF) viruses; therefore, targeting the TFs is key to control AIDS worldwide.

Gp120 is a glycosylated envelope protein required for HIV infection, propagation, and transmission. Glycans on gp120 influence HIV infectivity through their interactions with lectins, the carbohydrate-binding immune proteins in the host mucosa. To transmit sexually, viruses must overcome the lectin traps to access more target T cells.

Hypothesis:

TF viruses are less likely to …

A Human Papillomavirus-Independent Cervical Cancer Animal Model Reveals Unconventional Mechanisms Of Cervical Carcinogenesis, Chunbo He, Xiangmin Lv, Cong Huang, Peter C. Angeletti, Guohua Hua, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bowen Ma, Xingcheng Chen, Paul F. Lambert, Bo R. Rueda, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

HPV infections are common in healthy women and only rarely cause cervical cancer, suggesting that individual genetic susceptibility may play a critical role in the establishment of persistent HPV infection and the development of cervical cancer. Here, we provide convincing in vitro and in vivo evidence showing that differential expression and activation of YAP1 oncogene determine individual susceptibility to HPV infection and cervical carcinogenesis. We found that hyperactivation of YAP1 in mouse cervical epithelium was sufficient to induce invasive cervical cancer. Cervical epithelial cell-specific HPV16 E6/E7 and YAP1 double-knockin mouse model demonstrated that high-risk HPV synergized with hyperactivated YAP1 to …

Yap1-Lats2 Feedback Loop Dictates Senescent Or Malignant Cell Fate To Maintain Tissue Homeostasis, Chunbo He, Xiangmin Lv, Cong Huang, Guohua Hua, Bowen Ma, Xingcheng Chen, Peter C. Angeletti, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bo R. Rueda, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

Dysfunction of the homeostasis-maintaining systems in specific cell types or tissues renders the organism susceptible to a range of diseases, including cancers. One of the emerging mechanisms for maintaining tissue homeostasis is cellular senescence. Here, we report that the Hippo pathway plays a critical role in controlling the fate of ovarian cells. Hyperactivation of Yes-associated protein 1 (YAP1), the major effector of the Hippo pathway, induces senescence in cultured primary human ovarian surface epithelial cells (hOSEs). Large tumor suppressor 2 (LATS2), the primary upstream negative regulator of YAP1, is elevated in both YAP1-induced and natural replicative-triggered senescence. Deletion of LATS2 …

Near-Atomic Structure Of A Giant Virus, Qianglin Fang, Dongjie Zhu, Irina Agarkova, Jagat Adhikari, Thomas Klose, Yue Liu, Zhenguo Chen, Yingyuan Sun, Michael L. Gross, James L. Van Etten, Xinzheng Zhang, Michael G. Rossmann

Nebraska Center for Virology: Faculty Publications

Although the nucleocytoplasmic large DNA viruses (NCLDVs) are one of the largest group of viruses that infect many eukaryotic hosts, the near-atomic resolution structures of these viruses have remained unknown. Here we describe a 3.5 Å resolution icosahedrally averaged capsid structure of Paramecium bursaria chlorella virus 1 (PBCV-1). This structure consists of 5040 copies of the major capsid protein, 60 copies of the penton protein and 1800 minor capsid proteins of which there are 13 different types. The minor capsid proteins form a hexagonal network below the outer capsid shell, stabilizing the capsid by binding neighboring capsomers together. The size …

Design And Characterization Of A Consensus Hemagglutinin Vaccine Immunogen Against H3 Influenza A Viruses Of Swine, Haiyan Sun, Jung-Hyang Sur, Sarah Vitosh-Sillman, David J. Steffen, Hiep Vu

Nebraska Center for Virology: Faculty Publications

The substantial genetic diversity exhibited by influenza A viruses of swine (IAV-S) represents the main challenge for the development of a broadly protective vaccine against this important pathogen. The consensus vaccine immunogen has proven an effective vaccinology approach to overcome the extraordinary genetic diversity of RNA viruses. In this project, we sought to determine if a consensus IAV-S hemagglutinin (HA) immunogen would elicit broadly protective immunity in pigs. To address this question, a consensus HA gene (designated H3-CON.1) was generated from a set of 1,112 H3 sequences of IAV-S recorded in GenBank from 2011 to 2015. The consensus HA gene …

A Double Humanized Blt-Mice Model Featuring A Stable Human-Like Gut Microbiome And Human Immune System, Lance Daharsh, Jianshui Zhang, Amanda E. Ramer-Tait, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

Humanized mice (hu-mice) that feature a functional human immune system have fundamentally changed the study of human pathogens and disease. They can be used to model diseases that are otherwise difficult or impossible to study in humans or other animal models. The gut microbiome can have a profound impact on human health and disease. However, the murine gut microbiome is very different than the one found in humans. There is a need for improved pre-clinical hu-mice models that have an engrafted human gut microbiome. Therefore, we created double hu-mice that feature both a human immune system and stable human-like gut …

A Poxvirus Pseudokinase Represses Viral Dna Replication Via A Pathway Antagonized By Its Paralog Kinase, Annabel T. Olson, Zhigang Wang, Amber B. Rico, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Poxviruses employ sophisticated, but incompletely understood, signaling pathways that engage cellular defense mechanisms and simultaneously ensure viral factors are modulated properly. For example, the vaccinia B1 protein kinase plays a vital role in inactivating the cellular antiviral factor BAF, and likely orchestrates other pathways as well. In this study, we utilized experimental evolution of a B1 deletion virus to perform an unbiased search for suppressor mutations and identify novel pathways involving B1. After several passages of the ΔB1 virus we observed a robust increase in viral titer of the adapted virus. Interestingly, our characterization of the adapted viruses reveals that …

Relationship Between The Cervical Microbiome, Hiv Status, And Precancerous Lesions, Cameron Klein, Daniela Gonzalez, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, Nirosh Aluthge, Samodha Fernando, John T. West, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Nearly all cervical cancers are causally associated with human papillomavirus (HPV). The burden of HPV-associated dysplasias in sub-Saharan Africa is influenced by HIV. To investigate the role of the bacterial microbiome in cervical dysplasia, cytobrush samples were collected directly from cervical lesions of 144 Tanzanian women. The V4 hypervariable region of the 16S rRNA gene was amplified and deep sequenced. Alpha diversity metrics (Chao1, PD whole tree, and operational taxonomic unit [OTU] estimates) displayed significantly higher bacterial richness in HIV-positive patients (P = 0.01) than in HIV-negative patients. In HIV-positive patients, there was higher bacterial richness in patients with …

Persistent Viral Reservoirs In Lymphoid Tissues In Siv-Infected Rhesus Macaques Of Chinese-Origin On Suppressive Antiretroviral Therapy, Summer Siddiqui, Stefanie Perez, Yong Gao, Lara Doyle-Meyers, Brian T. Foley, Qingsheng Li, Binhua Ling

Nebraska Center for Virology: Faculty Publications

Understanding HIV latent reservoirs in tissues is essential for the development of new strategies targeting these sites for eradication. Here, we assessed the size of latent reservoirs and the source of residual viruses in multiple lymphoid tissues of SIV-infected and fully suppressed rhesus macaques of Chinese-origin (cRMs). Eight cRMs were infected with SIVmac251 and treated with tenofovir and emtricitabine daily for 24 weeks initiated 4 weeks post-infection. Four of the eight animals reached sustained full viral suppression with undetectable viremia. The levels of cell-associated SIV DNA varied in peripheral blood mononuclear cells (PBMCs) and multiple lymphoid tissues, but with higher …

A Single-Cycle Adenovirus Type 7 Vaccine For Prevention Of Acute Respiratory Disease, Brianna L. Bullard, Brigette N. Corder, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Adenovirus type 7 (Ad7) infection is associated with acute respiratory disease (ARD), especially in military recruits living in close quarters. Recently, several outbreaks of Ad7 infections have occurred in civilian populations, with some cases leading to death. However, the current Ad7 vaccine is licensed for use only in military recruits because it utilizes an orally delivered wild type virus which is shed in the stool for 28 days after immunization. This poses a safety risk due to the possibility of virus spread to vulnerable populations. To address the need for a safer Ad7 vaccine for use in civilian populations, we …

The Vaccinia Virus (Vacv) B1 And Cellular Vrk2 Kinases Promote Vacv Replication Factory Formation Through Phosphorylation-Dependent Inhibition Of Vacv B12, Annabel T. Olson, Zhigang Wang, Annabel Olson, Alexandria C. Linville, Brianna L. Bullard, Eric A. Weaver, Clinton Jones, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Comparative examination of viral and host protein homologs reveals novel mechanisms governing downstream signaling effectors of both cellular and vi- ral origin. The vaccinia virus B1 protein kinase is involved in promoting multiple facets of the virus life cycle and is a homolog of three conserved cellular enzymes called vaccinia virus-related kinases (VRKs). Recent evidence indicates that B1 and VRK2 mediate a com- mon pathway that is largely uncharacterized but appears independent of previous VRK substrates. Interestingly, separate studies described a novel role for B1 in inhibiting vac- cinia virus protein B12, which otherwise impedes an early event in the …

Efficacy Of A T Cell-Biased Adenovirus Vector As A Zika Virus Vaccine, Brianna L. Bullard, Brigette N. Corder, Matthew J. Gorman, Michael S. Diamond, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV) is a major public health concern due to the risk of congenital Zika syndrome in developing fetuses and Guillain-Barre syndrome in adults. Currently, there are no approved vaccines available to protect against infection. Adenoviruses are safe and highly immunogenic vaccine vectors capable of inducing lasting humoral and cellular immune responses. Here, we developed two Adenovirus (Ad) vectored Zika virus vaccines by inserting a ZIKV prM-E gene expression cassette into human Ad types 4 (Ad4-prM-E) and 5 (Ad5-prM-E). Immune correlates indicate that Ad5-prM-E vaccination induces both an anti-ZIKV antibody and T-cell responses whereas Ad4-prM-E vaccination only induces a …

Kaposi’S Sarcoma-Associated Herpesvirus Seropositivity Is Associated With Type 2 Diabetes Mellitus: A Case–Control Study In Xinjiang, China, Meng Cui, Qiwen Fang, Jun Zheng, Zhanjun Shu, Yin Chen, Yage Fan, Juan Zhao, Charles Wood, Tiejun Zhang, Yan Zeng

Nebraska Center for Virology: Faculty Publications

Objective: To assess the potential relationship between Kaposi’s sarcoma-associated herpesvirus (KSHV) infection and type 2 diabetes mellitus (DM-2) in Xinjiang, China.

Methods: A case–control study of consecutively included DM-2 patients and normal controls was conducted among the Uygur and Han populations in Xinjiang Uygur Autonomous Region, China. Blood samples were collected and KSHV seroprevalence, antibody titers, and viral load were investigated. Logistic regression analysis and multiple linear regression analysis were applied to explore determinants of the main outcome measures.

Results: A total of 324 patients with DM-2 and 376 normal controls were included. The seroprevalence of KSHV was 49.1% (95% …

Gene Gangs Of The Chloroviruses: Conserved Clusters Of Collinear Monocistronic Genes, Phillip Seitzer, Adrien Jeanniard, Fangrui Ma, James L. Van Etten, Marc T. Facciotti, David D. Dunigan

Nebraska Center for Virology: Faculty Publications

Chloroviruses (family Phycodnaviridae) are dsDNA viruses found throughout the world’s inland waters. The open reading frames in the genomes of 41 sequenced chloroviruses (330 + 40 kbp each) representing three virus types were analyzed for evidence of evolutionarily conserved local genomic “contexts”, the organization of biological information into units of a scale larger than a gene. Despite a general loss of synteny between virus types, we informatically detected a highly conserved genomic context defined by groups of three or more genes that we have termed “gene gangs”. Unlike previously described local genomic contexts, the definition of gene gangs requires only …

Susceptibility Genes To Plant Viruses, Hernan Garcia-Ruiz

Nebraska Center for Virology: Faculty Publications

Plant viruses use cellular factors and resources to replicate and move. Plants respond to viral infection by several mechanisms, including innate immunity, autophagy, and gene silencing, that viruses must evade or suppress. Thus, the establishment of infection is genetically determined by the availability of host factors necessary for virus replication and movement and by the balance between plant defense and viral suppression of defense responses. Host factors may have antiviral or proviral activities. Proviral factors condition susceptibility to viruses by participating in processes essential to the virus. Here, we review current advances in the identification and characterization of host factors …

Mechanisms Adopted By Dengue-2 Viruses To Induce Autophagy In Mammalian Cells, Sounak Ghosh Roy

Dissertations, Theses, and Capstone Projects

Dengue, the most rapidly spreading flavivirus, threatens to affect almost half of the human global population. We previously showed that dengue-2 protects canine kidney cells (MDCK) from cytotoxic chemicals. We showed, independently, that cell protection, as well as viral replication and maturation, are positively regulated by PI3K-dependent autophagy. However, we had not identified the specific pathway that induces autophagy in infected cells. The current study explores the role of a specific branch of the endoplasmic reticulum (ER) stress-mediated Unfolded Protein Response (UPR), the PERK/eIF2α/ATF4 pathway in the induction of autophagy by …

Type 2 Bovine Viral Diarrhea Virus NPro Suppresses Type I Interferon Pathway Signaling In Bovine Cells And Augments Bovine Respiratory Syncytial Virus Replication, Abdulrahman Abdulaziz A. Alkheraif

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Bovine viral diarrhea virus (BVDV) and bovine respiratory syncytial virus (BRSV) infections contribute to the bovine respiratory disease complex (BRDC), which is a multi-factorial disorder involving co-infections of viruses and bacteria including mycoplasma. BRDC causes great economic losses to the United States feedlot industry. BVDV infection induces immunosuppression in infected animals. BVDV N^pro binds and degrades the transcription factor interferon regulatory factor-3 (IRF-3) and effectively blocks type I interferon (type I IFN) expression in host cells. BRSV nonstructural proteins, NS1 and NS2, block activation of IRF-3. In calves, concurrent infection with BVDV and BRSV resulted in more severe clinical …

Brain Is A Potential Sanctuary For Subtype C Hiv-1 Irrespective Of Art Treatment Outcome, For Yue Tso, Guobin Kang, Eun Hee Kwon, Peter Julius, Qingsheng Li, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Subtype C HIV-1 is responsible for the largest proportion of people living with HIV-1 infection. However, there is limited information about the roles of the brain and its cell types as a potential sanctuary for this subtype and how the sanctuary may be affected by the administration of anti-retroviral therapy (ART). To address this issue, we collected postmortem brain tissues from ART treated HIV-1 infected Zambian individuals who experienced complete viral suppression and those who did not. Tissues from various brain compartments were collected from each individual as frozen and formalin-fixed paraffin embedded brain specimens, for detection and quantification of …

Altered Ratio Of T Follicular Helper Cells To T Follicular Regulatory Cells Correlates With Autoreactive Antibody Response In Simian Immunodeficiency Virus–Infected Rhesus Macaques, Wenjin Fan, Andrew James Demers, Yanmin Wan, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

Individuals with chronic HIV-1 infection have an increased prevalence of autoreactive Abs. Many of the isolated HIV broadly neutralizing Abs from these individuals are also autoreactive. However, the underlying mechanism(s) that produce these autoreactive broadly neutralizing Abs remains largely unknown. The highly regulated coordination among B cells, T follicular helper (T_FH) cells, and T follicular regulatory (T_FR) cells in germinal centers (GCs) of peripheral lymphatic tissues (LTs) is essential for defense against pathogens while also restricting autoreactive responses. We hypothesized that an altered ratio of T_FH/T_FR cells in the GC contributes to the …

Mucosal Antibody Responses To Vaccines Targeting Siv Protease Cleavage Sites Or Fulllength Gag And Env Proteins In Mauritian Cynomolgus Macaques, Hongzhao Li, Yan Hai, So-Yon Lim, Nikki Toledo, Jose Crecente-Campo, Dane Schalk, Lin Li, Robert W. Omange, Tamara G. Dacoba, Lewis R. Liu, Mohammad Abul Kashem, Yanmin Wan, Binhua Liang, Qingsheng Li, Eva Rakasz, Nancy Schultz-Darken, Maria J. Alonso, Francis A. Plummer, James B. Whitney, Ma Luo

Nebraska Center for Virology: Faculty Publications

HIV mutates rapidly and infects CD4⁺ T cells, especially when they are activated. A vaccine targeting conserved, essential viral elements while limiting CD4⁺ T cell activation could be effective. Learning from natural immunity observed in a group of highly HIV-1 exposed seronegative Kenyan female sex workers, we are testing a novel candidate HIV vaccine targeting the 12 viral protease cleavage sites (PCSs) (the PCS vaccine), in comparison with a vaccine targeting full-length Gag and Env (the Gag/Env vaccine) in a Mauritian cynomolgus macaque/SIV model. In this study we evaluated these vaccines for induction of mucosal antibodies to SIV …

Sivcpz Closely Related To The Ancestral Hiv-1 Is Less Or Non-Pathogenic To Humans In A Hu-Blt Mouse Model, Zhe Yuan, Guobin Kang, Lance Daharsh, Wenjin Fan, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

The HIV-1 pandemic is a consequence of the cross-species transmission of simian immunodeficiency virus in wild chimpanzees (SIVcpz) to humans. Our previous study demonstrated SIVcpz strains that are closely related to the ancestral viruses of HIV-1 groups M (SIVcpzMB897) and N (SIVcpzEK505) and two SIVcpz lineages that are not associated with any known HIV-1 infections in humans (SIVcpzMT145 and SIVcpzBF1167), all can readily infect and robustly replicate in the humanized-BLT mouse model of humans. However, the comparative pathogenicity of different SIVcpz strains remains unknown. Herein, we compared the pathogenicity of the above four SIVcpz strains with HIV-1 using humanized-BLT mice. …

Identification Of Unequally Represented Founder Viruses Among Tissues In Very Early Siv Rectal Transmission, Jian Chen, Yanqin Ren, Lance Daharsh, Lu Liu, Guobin Kang, Qingsheng Li, Qiang Wei, Yanmin Wu, Jianqing Xu

Nebraska Center for Virology: Faculty Publications

Characterizing the transmitted/founder (T/F) viruses of multi-variant SIV infection may shed new light on the understanding of mucosal transmission.We intrarectally inoculated six Chinese rhesus macaques with a single high dose of SIVmac251 (3.1 × 10⁴ TCID₅₀) and obtained 985 full-length env sequences from multiple tissues at 6 and 10 days post-infection by single genome amplification (SGA). All 6 monkeys were infected with a range of 2 to 8 T/F viruses and the dominant variants from the inoculum were still dominant in different tissues from each monkey. Interestingly, our data showed that a cluster of rare T/F viruses …