Vaccines, Blood & Biologics
Improving Safety of the Blood Supply from Transmission of HIV/AIDS and Other Emerging Blood Borne Viral and Biodefense Agents by Developing Sensitive Diagnostic Tools and Investigating Disease Pathogenesis
Principal Investigator: Indira Hewlett, PhD
Office / Division / Lab: OBRR / DETTD / LMV
HIV diagnostics and pathogenesis
HIV/AIDS is a global public health concern, with 33 million infections worldwide and several million deaths a year.
The virus is very diverse and new strains continue to emerge and spread rapidly worldwide. This poses challenges to diagnosing infected individuals and developing new vaccines and therapies. Therefore, it is imperative that FDA determine if newly developed tests for screening the blood supply for HIV accurately detect all the existing and emerging strains of the virus in blood samples. Our ongoing studies in Africa will help FDA in its global collaborations aimed at ensuring there are accurate HIV diagnostic tests and safe and effective vaccines available to respond to the changing population of AIDS viruses.
Our laboratory studies the factors that cause variations in the response of humans to HIV diversity. These studies will provide new insights that will support development of improved diagnosis, disease monitoring, drug design, and vaccines. We also helped to produce a new FDA document that offers guidance to blood donor facilities in identifying donors at increased risk for being infected with the variety of HIV-1 called "group O." This will help to screen out donors who might be infected based on having spent time in certain parts of Africa or having received blood transfusions or engaged in sexual activity with residents or former residents in those areas.
Novel detection technologies
Although testing for HIV has reduced the risk of transmitting the virus through donated blood, there are still three challenges to keeping the blood supply safe: 1) existing tests are performed only on plasma, while many agents are found mostly in blood cells; 2) testing requires large volumes and labor intensive instrumentation; and 3) existing tests cannot readily be modified to detect simultaneously the increasing number of infectious agents that pose new threats to the blood supply.
The goals of our work are to 1) develop new, improved diagnostic tools for testing blood and plasma and rapidly detecting emerging pathogens that threaten public health; and 2) provide FDA product reviewers with improved scientific understanding of novel technologies that might be applied by manufacturers, enhancing the review and evaluation of new diagnostic tests for blood-borne pathogens and bioterrorism agents.
Pandemic influenza and blood safety
Each year the FDA helps industry and international health agencies choose which influenza viruses will be represented by that year's "flu shot." FDA research also contributes to tests that determine the safety and potency of the vaccine. In addition to seasonal influenza there are other types of influenza of concern to FDA and other public health agencies.
H5N1 strains of avian influenza (bird flu) infect humans with a mortality rate close to 50%, much higher than the rate for seasonal influenza. Researchers have detected H5N1 in the blood of severely ill persons using very sensitive methods that can identify the genetic material of these pathogens. In 2009 another influenza virus called "swine flu" or H1N1, caused several hundred deaths in the US and spread quickly throughout the world.
Our group is developing assays as part of influenza pandemic preparedness. In collaboration with the FDA's Center for Devices and Radiological Health we are studying how the disease progresses, and how that progression is linked to the level of influenza viruses in the blood or nasal secretions. The major goal of this study is to determine whether influenza virus is present in blood in the asymptomatic phase, that is, when the infected individual is not showing evidence of disease. These data would help regulatory and public health officials to develop a blood screening policy that addresses donor deferral and product shortage issues during a pandemic if the virus is detected in the the blood of potential donors during the pre-symptomatic phase. In addition we are studying the correlation of the levels of flu virus genetic material with the ability of the virus to infect humans using animals as models of this infection. The laboratory also contributed significantly to developing a document that provides industry with guidance and recommendations for the assessment of donor suitability and blood product safety with regard to pandemic influenza
XMRV and blood safety
In 2006, the human retrovirus XMRV (xenotropic murine leukemia virus-related virus) was identified and reported to be associated with certain cases of prostate cancer and, more recently, scientists have shown an association with chronic fatigue syndrome (CFS). XMRV has also been found in about 4% of healthy individuals.
The results of various studies suggest that people infected with XMRV carry the virus in their blood stream. This raises public health concerns that such individuals could spread the virus through blood donations. Therefore, our laboratory is developing sensitive ways to test for XMRV in blood and to test the accuracy of assays used by different laboratories to diagnose infection with XMRV. This work will help to prepare blood collection centers for testing blood for this virus in the event that it becomes necessary in order to ensure the safety of the blood supply.
These tools will also help public health officials and researchers to collect data on the prevalence and distribution of XMRV and to study infection and transmission of the virus.
Therefore, we plan to develop in-house tests to detect the virus, the immune response to the virus, and its genetic material. Our laboratory also hopes to study the prevalence of XMRV in other parts of the world, such as Cameroon in African, where similar types of viral infections are known to be prevalent. We also plan to investigate the ability of the virus to infect hematopoietic cells, which are the parent cells that give rise to the various blood cells.
We obtained plasma and viruses representing major new strains from Cameroon, where all diverse HIV strains are prevalent and new strains continue to emerge. Our laboratory uses these samples to evaluate new antibody/antigen and nucleic acid tests (NAT) designed to detect and quantify these strains. We use gene sequencing to identify strains, tropism, and drug resistance. Correlation of sequencing data with cell-based phenotyping for tropism will provide FDA with valuable experience with this emerging class of products. The laboratory now plans to use new, high throughput, ultra-deep sequencing techniques to characterize virus genetic material.
Although most samples were detected by FDA licensed assays, NAT assays only inconsistently detected some CRF02_AG and CRF01_AE specimens. Therefore, we tested these strains in a collaborative study. New reference panels of these viruses were prepared to help FDA evaluate licensed and new NAT assays to detect them.
Our laboratory is also using in vitro cell culture systems and molecular genomics to study the impact of strain diversity, sex hormone effects, host genetics and cell signaling pathways on viral pathogenesis.
Novel detection technologies
We use nanoparticles in ELISA rapid or microarray formats as proof-of-concept strategies to improve assays. Gold nanoparticles coupled with silver enhanced detection of HIV-1 p24 antigen by approximately 100-150-fold compared to the conventional ELISA format. Fluorescent europium (Eu+) nanoparticles (NP) reduced assay time while achieving similar levels of sensitivity. Europium nanoparticles also enhanced detection of anthrax 50-100 fold, allowing earlier detection of the toxin than was previously possible. We showed that nanoparticles offer remarkable improvements in the sensitivity of protein-based assays for pathogens and might provide improved diagnostic tools for pathogens in the future.
Our laboratory is also evaluating non-PCR nanoparticle-based genomic microarray NAT techniques that achieve PCR-like detection limits without using enzymes or PCR amplification. West Nile Virus (WNV) RNA detection was comparable to PCR using these arrays. We detected Ebola, Marburg and Lassa viruses with a high degree of sensitivity using this approach and successfully used it for multiplexed detection and genotyping of major influenza viruses, including H1N1, H3N2 and H5N1. The signals in this assay could be visually read by enhancement with silver staining allowing adaptation to rapid detection formats. Our work clearly demonstrates the potential for nanotechnology to provide new, rapid and sensitive diagnostics for pathogens.
Pandemic influenza and blood safety
We determined the presence of virus in the blood of ferrets and mice infected with different doses of H5N1 virus, collecting blood, lungs, nasal washes, nasal turbinates and brain at different time points. Sensitive taqMan and virus culture assays are being used to measure virus in blood and the various tissues. We are planning to inoculate H5N1 and 2009 H1N1 intravenously into ferrets and mice to determine transmissibility and pathogenesis of virus if transmitted through the intravenous route, simulating transfusion.
Our preliminary findings indicate that viremia in H5N1 infection can be detected at the onset of symptoms and is generally associated with fatal outcomes in ferrets. Similar studies are underway with H1N1 infection. In a separate study we tested plasma from 300 blood donors using sensitive Taqman assays for H1N1 and have so far found no positive samples in this sample set. These findings are important in our understanding of influenza viremia and its detectability in blood donors.
XMRV and blood safety
In 2006, the human retrovirus XMRV (xenotropic murine leukemia virus-related virus) was identified and reported to be associated with certain cases of prostate cancer and, more recently, with chronic fatigue syndrome (CFS). XMRV has also been found in about 4% of healthy individuals.
Studies have shown that XMRV infects T and B cells, and transient viremia has been detected in animals after infection with XMRV. In addition, virus from plasma was able to infect susceptible cells, suggesting that infectious virus is present in the blood stream. This raises public health concerns about the safety of the blood supply. It is therefore critical to develop sensitive test methods and well-characterized reference reagents to standardize assays from different labs and ensure the accuracy of diagnostic findings. The reference panels will be used for lot release testing of kits in the event testing of the blood supply becomes necessary. These tools will also be needed to perform studies of prevalence, distribution, virus infectivity, and transmission, to clarify and corroborate the findings of XMRV that have been reported so far. Current data on prevalence in the general population is primarily derived from a restricted geographic locations in the US; additional studies are needed to examine prevalence on other populations.
Patient-derived XMRV has been shown to be infectious, and both cell-associated and cell-free transmission of the virus is possible, and a study in rhesus macaques indicated a viremic phase. These findings point to a new transfusion threat that needs further investigation.
Therefore, we proposed to 1) develop in-house Taqman, antigen and antibody assays to detect the virus and its immune responses; 2) develop reference panels for detection of nucleic acid, and antibody, 3) study prevalence in other settings including Cameroon in Africa where other retroviral infections are known to be prevalent; and 4) investigate infectivity and tropism of the virus for hematopoietic cells in cell culture systems and appropriate animal models.
We have developed sensitive Taqman assays based on primers from the gag region to make it specific for XMRV. In addition, we are obtaining infectious clones, virus isolates, recombinant proteins, and antibodies for further characterization in a collaborative study based on sequence analysis and evaluation of reactivity using tests developed at CBER and other laboratories in a collaborative study.
For the nucleic acid test (NAT) panel, we provided laboratories with virus preparations diluted in plasma for testing. Results of all labs will be evaluated statistically to obtain a consensus value. For antibody panels, reactivity of candidate materials will be tested in multiple laboratories to determine the suitability of the material for use as a reference reagent. The assays will be used to test samples previously obtained from donors in Cameroon for the presence of XMRV sequences by NAT or antibodies by ELISA. Various T and B cell lines, monocytes, and PBMCs will be infected with different concentrations of the virus to evaluate infectivity. Transmissibility of cell-free and cell-associated virus between lymphoid cells and indicator cells will be studied. Rhesus macaque studies will be performed to study the natural history of the virus and secondary transmission through transfusion. Samples collected at various time points after infection can also serve as useful reagents to assess the sensitivity of assays and as future reference reagents.
The proposed studies are expected to provide the following outcomes: 1) optimizing in-house assays for studies of XMRV prevalence, transmission, and pathogenesis; 2) developing reference reagents for standardization of XMRV assays based on NAT or antibody and animal derived seroconversion panels for sensitivity evaluation; 3) identifying seroprevalence in persons from different geographic regions; 4) gaining new knowledge of cell tropism, transmissibility, and infectivity for blood cells using in vitro cell culture systems; and 5) evaluating infectivity, transmissibility, and pathogenesis of the virus using susceptible animal models.
Viruses 2015 Feb 5;7(2):543-58
HIV-1 Induced Nuclear Factor I-B (NF-IB) Expression Negatively Regulates HIV-1 Replication through Interaction with the Long Terminal Repeat Region.
Vemula SV, Veerasamy R, Ragupathy V, Biswas S, Devadas K, Hewlett I
Biosens Bioelectron 2014 Nov 15;61:177-83
Development of a microchip Europium nanoparticle immunoassay for sensitive point-of-care HIV detection.
Liu J, Du B, Zhang P, Haleyurgirisetty M, Zhao J, Ragupathy V, Lee S, DeVoe DL, Hewlett IK
PLoS One 2014 Nov 7;9(11):e112434
Genotypic Prediction of Tropism of Highly Diverse HIV-1 Strains from Cameroon.
Mbondji-Wonje C, Ragupathy V, Zhao J, Nanfack A, Lee S, Torimiro J, Nyambi P, Hewlett IK
Nat Commun 2014 Oct 6;5:5079
Quantification of plasma HIV RNA using chemically engineered peptide nucleic acids.
Zhao C, Hoppe T, Setty MK, Murray D, Chun TW, Hewlett I, Appella DH
Mol Cell Biochem 2014 Aug;393(1-2):181-90
Some findings of FADD knockdown in inhibition of HIV-1 replication in Jurkat cells and PBMCs.
Wang X, Tan J, Zhao J, Ragupathy V, Haleyurgirisetty M, Hewlett I
BMC Infect Dis 2014 Apr 8;14:192
Highly pathogenic avian influenza A virus (H5N1) can be transmitted in ferrets by transfusion.
Wang X, Tan J, Zhao J, Ye Z, Hewlett I
Microbes Infect 2014 Mar;16(3):178-86
Novel pandemic influenza A (H1N1) virus infection modulates apoptotic pathways that impact its replication in A549 cells.
Wang X, Tan J, Zoueva O, Zhao J, Ye Z, Hewlett I
J Med Virol 2014 Mar;86(3):385-93
The evolution of HIV-1 group M genetic variability in Southern Cameroon is characterized by several emerging recombinant forms of CRF02_AG and viruses with drug resistance mutations.
Agyingi L, Mayr LM, Kinge T, Orock GE, Ngai J, Asaah B, Mpoame M, Hewlett I, Nyambi P
AIDS Res Treat 2014;2014:497046
Point of Care Technologies for HIV.
Haleyur Giri Setty MK, Hewlett IK
J Cell Physiol 2013 Dec;228(12):2305-13
Some mechanisms of FLIP expression in inhibition of HIV-1 replication in Jurkat cells, CD4+ T cells and PBMCs.
Tan J, Wang X, Devadas K, Zhao J, Zhang P, Hewlett I
J Steroid Biochem Mol Biol 2013 Nov;138:63-71
Effect of sex steroid hormones on replication and transmission of major HIV subtypes.
Ragupathy V, Devadas K, Tang S, Wood O, Lee S, Dastyer A, Wang X, Dayton A, Hewlett I
Viruses 2013 Sep 19;5(9):2253-9
Seroprevalence of human herpesvirus-8 in HIV-1 infected and uninfected individuals in Cameroon.
Mbondji-Wonje C, Ragupathy V, Lee S, Wood O, Awazi B, Hewlett IK
Viruses 2012 Nov 9;4(11):3012-9
Rapid detection and differentiation of swine-origin influenza A virus (H1N1/2009) from other seasonal influenza A viruses.
Zhao J, Wang X, Ragupathy V, Zhang P, Tang W, Ye Z, Eichelberger M, Hewlett I
J Acquir Immune Defic Syndr 2012 Aug 1;60(4):344-50
CRF22_01A1 is involved in the emergence of new HIV-1 recombinants in Cameroon.
Zhao J, Tang S, Ragupathy V, Gaddam D, Wang X, Zhang P, Nyambi PN, Hewlett I
Cell Signal 2012 Jul;24(7):1414-9
HIV-1 and HIV-2 infections induce autophagy in Jurkat and CD4+ T cells.
Wang X, Gao Y, Tan J, Devadas K, Ragupathy V, Takeda K, Zhao J, Hewlett I
AIDS Res Hum Retroviruses 2012 Jun;28(6):594-606
Pilot Studies for Development of an HIV Subtype Panel for Surveillance of Global Diversity.
Manak M, Sina S, Anekella B, Hewlett I, Sanders-Buell EE, Ragupathy V, Kim JH, Vermeulen M, Stramer S, Sabino E, Grabarczyk P, Michael NL, Peel S, Garrett PE, Tovanabutra S, Busch M, Schito M
J Infect Dis 2012 Mar;205(6):886-894
Sensitive Detection Assays for Influenza RNA Do Not Reveal Viremia in US Blood Donors.
Stramer SL, Collins C, Nugent T, Wang X, Fuschino M, Heitman JW, Law J, Krysztof DE, Kiely N, Todd D, Vermeulen NM, Harrington K, Kamel H, Kelvin DJ, Busch MP, St George K, Hewlett IK, Linnen JM, Norris PJ, NHLBI Retrovirus Epidemiology Donor Study-II (REDS-II)
PLoS One 2012;7(3):e32853
Identification of XMRV infection-associated microRNAs in four cell types in culture.
Mohan KV, Devadas K, Sainath Rao S, Hewlett I, Atreya C
Infect Immun 2012 Feb;80(2):529-38
Anthrax edema toxin impairs clearance in mice.
Sastalla I, Tang S, Crown D, Liu S, Eckhaus MA, Hewlett IK, Leppla SH, Moayeri M
Virology 2011 Dec 20;421(2):253-65
The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability.
Jiang J, Ablan SD, Derebail S, Hercík K, Soheilian F, Thomas JA, Tang S, Hewlett I, Nagashima K, Gorelick RJ, Freed EO, Levin JG
BMC Infect Dis 2011 Dec 22;11:354
Stability and infectivity of novel pandemic influenza A (H1N1) virus in blood-derived matrices under different storage conditions.
Wang X, Zoueva O, Zhao J, Ye Z, Hewlett I
PLoS One 2011;6(11):e27391
Absence of detectable XMRV and other MLV-related viruses in healthy blood donors in the United States.
Tang S, Zhao J, Haleyur Giri Setty MK, Devadas K, Gaddam D, Viswanath R, Wood O, Zhang P, Hewlett IK
Science 2011 Nov 11;334(6057):814-7
Failure to confirm XMRV/MLVs in the blood of patients with chronic fatigue syndrome: a multi-laboratory study.
Simmons G, Glynn SA, Komaroff AL, Mikovits JA, Tobler LH, Hackett J Jr, Tang N, Switzer WM, Heneine W, Hewlett IK, Zhao J, Lo SC, Alter HJ, Linnen JM, Gao K, Coffin JM, Kearney MF, Ruscetti FW, Pfost MA, Bethel J, Kleinman S, Holmberg JA, Busch MP, Blood XMRV Scientific Research Working Group (SRWG)
Biochem Biophys Res Commun 2011 Oct 14;414(1):20-4
Molecules from apoptotic pathways modulate HIV-1 replication in Jurkat cells.
Wang X, Ragupathy V, Zhao J, Hewlett I
Virol J 2011 Sep 20;8:443
Susceptibility of human primary neuronal cells to xenotropic murine leukemia virus-related (XMRV) virus infection.
Ravichandran V, Major EO, Ibe C, Monaco MC, Girisetty MK, Hewlett IK
Virol J 2011 Sep 6;8:423
XMRV: usage of receptors and potential co-receptors.
Haleyur Giri Setty MK, Devadas K, Ragupathy V, Ravichandran V, Tang S, Wood O, Gaddam DS, Lee S, Hewlett IK
Advances in Virology 2011;2011:281425
Testing strategies for detection of xenotropic murine leukemia virus-related virus infection.
Tang S, Hewlett IK
Med Chem Res 2011 Apr;20(3):314-20
Screening and evaluation of thiourea derivatives for their HIV capsid and human cyclophilin A inhibitory activity
Tan ZW, Li JB, Pang RF, He SS, He MZ, Tang SX, Hewlett I, Yang M
Virol J 2011 Apr 23;8(1):185
Identification of new, emerging HIV-1 unique recombinant forms and drug resistant viruses circulating in Cameroon.
Ragupathy V, Zhao J, Wood O, Tang S, Lee S, Nyambi P, Hewlett I
Transfusion 2011 Mar;51(3):463-8
Absence of detectable xenotropic murine leukemia virus-related virus in plasma or peripheral blood mononuclear cells of human immunodeficiency virus Type 1-infected blood donors or individuals in Africa.
Tang S, Zhao J, Viswanath R, Nyambi PN, Redd AD, Dastyar A, Spacek LA, Quinn TC, Wang X, Wood O, Gaddam D, Devadas K, Hewlett IK
Chem Biol Drug Des 2011 Mar;77(3):189-98
Synthesis and Antiviral Evaluation of New N-acylhydrazones Containing Glycine Residue.
Tian B, He M, Tan Z, Tang S, Hewlett I, Chen S, Jin Y, Yang M
Transfusion 2011 Mar;51(3):643-53
The Blood Xenotropic Murine Leukemia Virus-Related Virus Scientific Research Working Group: mission, progress, and plans.
Simmons G, Glynn SA, Holmberg JA, Coffin JM, Hewlett IK, Lo SC, Mikovits JA, Switzer WM, Linnen JM, Busch MP, Blood XMRV Scientific Research Working Group
BMC Biotechnol 2010 Oct 13;10:74
Multiplexed, rapid detection of H5N1 using a PCR-free nanoparticle-based genomic microarray assay.
Zhao J, Tang S, Storhoff J, Marla S, Bao YP, Wang X, Wong EY, Ragupathy V, Ye Z, Hewlett IK
Anal Chem 2010 Oct 15;82(20):8406-11
Ultrasensitive Detection of HIV-1 p24 Antigen Using Nanofunctionalized Surfaces in a Capacitive Immunosensor.
Teeparuksapun K, Hedstrom M, Wong EY, Tang S, Hewlett IK, Mattiasson B
AIDS Res Hum Retroviruses 2010 Sep;26(9):1033-45
Identification and Genetic Characterization of a Novel CRF22_01A1 Recombinant Form of HIV Type 1 in Cameroon.
Zhao J, Tang S, Ragupathy V, Carr JK, Wolfe ND, Awazi B, Hewlett I
Clin Vaccine Immunol 2010 Aug;17(8):1244-51
Characterization of immune responses to capsid protein p24 of human immunodeficiency virus type 1 and implications for detection.
Tang S, Zhao J, Wang A, Viswanath R, Harma H, Little RF, Yarchoan R, Stramer SL, Nyambi PN, Lee S, Wood O, Wong EY, Wang X, Hewlett IK
PLoS One 2010 Aug 12;5(8):e12099
Viremia associated with fatal outcomes in ferrets infected with avian H5N1 influenza virus.
Wang X, Zhao J, Tang S, Ye Z, Hewlett I
Chem Biol Drug Des 2010 Jul;76(1):25-33
Structure-Activity Relationships (SAR) Research of Thiourea Derivatives as Dual Inhibitors Targeting both HIV-1 Capsid and Human Cyclophilin A.
Chen K, Tan Z, He M, Li J, Tang S, Hewlett I, Yu F, Jin Y, Yang M
J Leukoc Biol 2010 May;87(5):915-24
Lipopolysaccharide suppresses HIV-1 replication in human monocytes by protein kinase C-dependent heme oxygenase-1 induction.
Devadas K, Hewlett IK, Dhawan S
Mol Cell Biochem 2010 Apr;337(1-2):175-83
Changes in the level of apoptosis-related proteins in Jurkat cells infected with HIV-1 versus HIV-2.
Wang X, Viswanath R, Zhao J, Tang S, Hewlett I
Bioorg Med Chem 2010 Mar 15;18(6):2135-40
SAR and molecular mechanism study of novel acylhydrazone compounds targeting HIV-1 CA.
Jin Y, Tan Z, He M, Tian B, Tang S, Hewlett I, Yang M
J Med Virol 2010 Feb;82(2):187-96
HIV-1 reverse transcriptase drug-resistance mutations in chronically infected individuals receiving or naive to HAART in Cameroon.
Burda ST, Viswanath R, Zhao J, Kinge T, Anyangwe C, Tinyami ET, Haldar B, Powell RL, Jarido V, Hewlett IK, Nyambi PN
AIDS Res Ther 2009 Nov 25;6:27
Comparative analysis of cell culture and prediction algorithms for phenotyping of genetically diverse HIV-1 strains from Cameroon.
Ragupathy V, Zhao J, Wang X, Wood O, Lee S, Burda S, Nyambi P, Hewlett I
Mol Cell Biochem 2009 Oct;330(1-2):23-9
c-FLIPL regulates PKC via AP-2 to inhibit Bax-mediated apoptosis induced by HIV-1 gp120 in Jurkat cells.
Wang X, Zhao J, Tang S, Lee S, Glazer RI, Hewlett I
Bioorg Med Chem Lett 2009 Apr 15;19(8):2162-7
Synthesis and antiviral activities of novel acylhydrazone derivatives targeting HIV-1 capsid protein.
Tian B, He M, Tang S, Hewlett I, Tan Z, Li J, Jin Y, Yang M
Bioorg Med Chem 2009 Apr 15;17(8):3177-88
Discovery of dual inhibitors targeting both HIV-1 capsid and human cyclophilin A to inhibit the assembly and uncoating of the viral capsid.
Li J, Tan Z, Tang S, Hewlett I, Pang R, He M, He S, Tian B, Chen K, Yang M
Clin Vaccine Immunol 2009 Mar;16(3):408-13
Detection of anthrax toxin by an ultrasensitive immunoassay using europium nanoparticles.
Tang S, Moayeri M, Chen Z, Harma H, Zhao J, Hu H, Purcell RH, Leppla SH, Hewlett IK
J Infect Dis 2008 Nov 1;198(9):1300-8
In Vitro Evaluation of the Protective Role of Human Antibodies to West Nile Virus (WNV) Produced during Natural WNV Infection.
Rios M, Daniel S, Dayton AI, Wood O, Hewlett IK, Epstein JS, Caglioti S, Stramer SL
J Acquir Immune Defic Syndr 2007 Oct 1;46(2):231-7
Nanoparticle-Based Biobarcode Amplification Assay (BCA) for Sensitive and Early Detection of Human Immunodeficiency Type 1 Capsid (p24) Antigen.
Tang S, Zhao J, Storhoff JJ, Norris PJ, Little RF, Yarchoan R, Stramer SL, Patno T, Domanus M, Dhar A, Mirkin CA, Hewlett IK
AIDS Res Hum Retroviruses 2007 Oct;23(10):1262-7
Detection of Emerging HIV Variants in Blood Donors from Urban Areas of Cameroon.
Lee S, Wood O, Tang S, Hu J, Machuca A, Kerby S, Awazi B, Vockley C, Hewlett I
AIDS Res Hum Retroviruses 2007 Aug;23(8):1008-19
Identification of a Novel Circulating Recombinant Form (CRF) 36_cpx in Cameroon That Combines Two CRFs (01_AE and 02_AG) with Ancestral Lineages of Subtypes A and G.
Powell RL, Zhao J, Konings FA, Tang S, Nanfack A, Burda S, Urbanski MM, Saa DR, Hewlett I, Nyambi PN
Clin Infect Dis 2007 Jul 15;45(2):181-6
West nile virus adheres to human red blood cells in whole blood.
Rios M, Daniel S, Chancey C, Hewlett IK, Stramer SL
J Acquir Immune Defic Syndr 2007 Jul 1;45(3):361-3
Increased Genetic Diversity and Intersubtype Recombinants of HIV-1 in Blood Donors From Urban Cameroon.
Machuca A, Tang S, Hu J, Lee S, Wood O, Vockley C, Vutukuri SG, Deshmukh R, Awazi B, Hewlett I
AIDS Res Hum Retroviruses 2007 Jul;23(7):923-33
Circulating recombinant form (CRF) 37_cpx: an old strain in Cameroon composed of diverse, genetically distant lineages of subtypes A and G.
Powell RL, Zhao J, Konings FA, Tang S, Ewane L, Burda S, Urbanski MM, Saa DR, Hewlett I, Nyambi PN
Biochem Biophys Res Commun 2007 May 18;356(4):1017-23
Microarray multiplex assay for the simultaneous detection and discrimination of hepatitis B, hepatitis C, and human immunodeficiency type-1 viruses in human blood samples.
Hsia CC, Chizhikov VE, Yang AX, Selvapandiyan A, Hewlett I, Duncan R, Puri RK, Nakhasi HL, Kaplan GG
Virology 2007 Mar 1;359(1):105-15
A second-site suppressor significantly improves the defective phenotype imposed by mutation of an aromatic residue in the N-terminal domain of the HIV-1 capsid protein.
Tang S, Ablan S, Dueck M, Ayala-Lopez W, Soto B, Caplan M, Nagashima K, Hewlett IK, Freed EO, Levin JG
Peptides 2007 Mar;28(3):496-504
Antibodies against a multiple-peptide conjugate comprising chemically modified human immunodeficiency virus type-1 functional Tat peptides inhibit infection.
Devadas K, Boykins RA, Hewlett IK, Wood OL, Clouse KA, Yamada KM, Dhawan S
J Virol Methods 2006 Nov;137(2):287-91
Development and evaluation of HIV-1 subtype RNA panels for the standardization of HIV-1 NAT assays.
Lee S, Wood O, Taffs RE, Hu J, Machuca A, Vallejo A, Hewlett I
J Acquir Immune Defic Syndr 2006 Nov 1;43(3):304-12
Novel Approach for Differential Diagnosis of HIV Infections in the Face of Vaccine-Generated Antibodies: Utility for Detection of Diverse HIV-1 Subtypes.
Khurana S, Needham J, Park S, Mathieson B, Busch MP, Nemo G, Nyambi P, Zolla-Pazner S, Laal S, Mulenga J, Chomba E, Hunter E, Allen S, McIntyre J, Hewlett I, Lee S, Tang S, Cowan E, Beyrer C, Altfeld M, Yu XG, Tounkara A, Koita O, Kamali A, Nguyen N, Graham BS, Todd D, Mugenyi P, Anzala O, Sanders E, Ketter N, Fast P, Golding H
Transfusion 2006 Oct;46(10):1847-8
Performance of serological assays used to test blood from recent smallpox vaccinees.
Srinivasan K, Lee S, Daniel S, Wood O, Akolkar P, Hewlett I
Transfusion 2006 Sep;46(9):1647-8
Serologic testing for human T-lymphotropic virus-3 and -4.
Switzer WM, Hewlett I, Aaron L, Wolfe ND, Burke DS, Heneine W
Transfusion 2006 Sep;46(9):1589-92
Absence of detectable viremia in plasma and peripheral blood mononuclear cells from smallpox vaccinees: implications for blood safety.
Srinivasan K, Akolkar PN, Taffs RE, Hewlett IK
Peptides 2006 Apr;27(4):611-21
Selective side-chain modification of cysteine and arginine residues blocks pathogenic activity of HIV-1-Tat functional peptides.
Devadas K, Boykins RA, Hardegen NJ, Philp D, Kleinman HK, Osa EO, Wang J, Clouse KA, Wahl LM, Hewlett IK, Rappaport J, Yamada KM, Dhawan S
Transfusion 2006 Apr;46(4):659-67
Monocytes-macrophages are a potential target in human infection with West Nile virus through blood transfusion.
Rios M, Zhang MJ, Grinev A, Srinivasan K, Daniel S, Wood O, Hewlett IK, Dayton AI
J Med Virol 2006 Apr 18;78(S1):S22-S23
Evaluation of FDA licensed HIV assays using plasma from Cameroonian blood donors.
Lee S, Hu J, Tang S, Wood O, Francis K, Machuca A, Rios M, Daniel S, Vockley C, Awazi B, Zekeng L, Hewlett I
Clin Infect Dis 2005 Jun 1;40(11):1673-6
Seroprevalence of human T cell leukemia virus in HIV antibody-negative populations in rural Cameroon.
Machuca A, Wood O, Lee S, Daniel S, Rios M, Wolfe ND, Carr JK, Eitel MN, Tamoufe U, Torimiro JN, Burke D, Hewlett IK
J Immunol 2004 Dec 1;173(11):6735-44
Mechanisms for Macrophage-Mediated HIV-1 Induction.
Devadas K, Hardegen NJ, Wahl LM, Hewlett IK, Clouse KA, Yamada KM, Dhawan S
Transfusion 2004 Jun;44(6):929-33
Window-period human immunodeficiency virus transmission to two recipients by an adolescent blood donor.
Phelps R, Robbins K, Liberti T, Machuca A, Leparc G, Chamberland M, Kalish M, Hewlett I, Folks T, Lee LM, McKenna M
AIDS Res Hum Retroviruses 2004 May;20(5):507-12
HIV Type 2 Primary Isolates Induce a Lower Degree of Apoptosis "in Vitro" Compared with HIV Type 1 Primary Isolates.
Machuca A, Ding L, Taffs R, Lee S, Wood O, Hu J, Hewlett I