publications

Opioid use disorder (OUD) and opioid overdoses are public health emergencies. In 2021, 80,000 opioid overdose associated deaths were reported in the United States. Despite the availability of treatment strategies, including medications for opioid use disorder (MOUD) and naloxone, opioid overdoses continue to increase at an alarming rate. Opioid vaccines are a novel approach to combat the growing crisis with several candidates recently entering human clinical trials. In this study, we investigated Qβ bacteriophage virus-like particles (VLPs) as a vaccine platform for immunogenic display of oxycodone. A derivative of oxycodone was conjugated to pre-formed Qβ VLPs using a sulfhydryl-amine reactive heterobifunctional crosslinker with high loading of oxycodone. In mice, intramuscular immunization with Qβ-oxycodone elicited high-titer, high-avidity and long-lasting antibody responses. Qβ-oxycodone was also immunogenic after storage at ambient room temperature for over two weeks, demonstrating that the vaccine is highly thermostable. In mice, immunization with Qβ-oxycodone elicited antibodies that sequester oxycodone in the serum, an important mechanism for preventing the adverse effects of opioid activity. Finally, Qβ-oxycodone is immunogenic in nonhuman primates, eliciting serum oxycodone antibodies after intramuscular immunization of rhesus macaques. These data establish Qβ-oxycodone as a promising opioid vaccine candidate.

The COVID-19 pandemic, although a profound reminder of endured injustices by and the disparate impact of infectious diseases on Indigenous populations, has also served as an example of Indigenous strength and the ability to thrive anew. Many infectious diseases share common risk factors that are directly tied to the ongoing effects of colonisation. We provide historical context and case studies that illustrate both challenges and successes related to infectious disease mitigation in Indigenous populations in the USA and Canada. Infectious disease disparities, driven by persistent inequities in socioeconomic determinants of health, underscore the urgent need for action. We call on governments, public health leaders, industry representatives, and researchers to reject harmful research practices and to adopt a framework for achieving sustainable improvements in the health of Indigenous people that is both adequately resourced and grounded in respect for tribal sovereignty and Indigenous knowledge.

The fungal disease Valley fever causes a significant medical and financial burden for affected people in the endemic region, and this burden is on the rise. Despite the medical importance of this disease, little is known about ecological factors that influence the geographic point sources of high abundance of the pathogens Coccidioides posadasii and C. immitis, such as competition with co-occurring soil microbes. These “hot spots”, for instance, those in southern Arizona, are areas in which humans are at greater risk of being infected with the fungus due to consistent exposure. The aim of this study was to isolate native microbes from soils collected from Tucson, Arizona (endemic area for C. posadasii) and characterize their relationship (antagonistic, synergistic, or neutral) to the fungal pathogen with in vitro challenge assays. Secreted metabolites from the microbes were extracted and described using analytical techniques including high-performance liquid chromatography (HPLC) and mass spectrometry. Bacteria belonging to the genus Bacillus and fungi in the Fennellomyces and Ovatospora genera were shown to significantly decrease the growth of Coccidioides spp. In vitro. In contrast, other bacteria in the Brevibacillus genus, as well as one species of Bacillus bacteria, were shown to promote growth of Coccidioides when directly challenged. The metabolites secreted from the antagonistic bacteria were described using HPLC and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The microbes identified in this study as antagonists to Coccidioides and/or the metabolites they secrete have the potential to be used as natural biocontrol agents to limit the amount of fungal burden at geographic point sources, and therefore limit the potential for human infection.

Indigenous and American Indian Alaskan Native (AI/AN) community members are systematically underrepresented in clinical trial research. This paper focuses on exploratory steps to partner with Native Nations of Arizona to engage Community Health Representatives (CHR) as a trusted source for building COVID-19 clinical trial research, including vaccine trials awareness. CHRs are frontline public health workers who apply a unique understanding of the experience, language, and culture of the population served. This workforce has entered the spotlight as essential to the prevention and control of COVID-19. Methods: Three Tribal CHR programs were engaged to develop and refine culturally centered educational materials and a pre-post survey using a consensus-based decision-making approach. CHRs used these materials in brief education sessions during regular client home visits and community events. Results: At 30 days post CHR intervention, participants (N = 165) demonstrated significantly increased awareness about and ability to enroll in COVID-19 treatment and vaccine trials. Participants also described a significant increase in trust in researchers, decreased perceived barriers related to cost for participation in a clinical trial, and improved belief that participation in a COVID-19 clinical trial for treatment was considered a benefit to American Indian and Alaskan Native people. Conclusion: CHRs as trusted sources of information, coupled with culturally centered education materials designed by CHRs for CHR clients, demonstrated a promising approach to improved awareness of clinical trial research generally and COVID-19 trials specifically among Indigenous and American Indian community members of Arizona.

The COVID-19 pandemic has both highlighted and worsened existing health inequities among communities of color and structurally vulnerable populations. Community Health Workers, inclusive of Community Health Representatives (CHW/Rs) have entered the spotlight as essential to COVID-19 prevention and control. To learn about community experiences and perspectives related to COVID-19 and inform CHW/R workforce capacity building efforts, a series of focus groups were conducted with CHW/Rs throughout Arizona at two time points in 2021. Throughout the data collection and analysis process, researchers and community partners engaged in ongoing and open dialogue about what CHW/Rs on the ground were reporting as priority community concerns, needs, and challenges. Thus, CHW/Rs informed the development of culturally and linguistically relevant health education messages, materials, and training for CHW/Rs. In this community case study, we detail the efforts of partnership between a statewide CHW professional association and an academic research team that facilitated rapid decision-making and knowledge sharing to create community-grounded tools and resources supportive of CHW/R workforce capacity building in the context of the COVID-19 pandemic.

The goal of this study was to establish effective, culturally appropriate strategies to enhance participation of American Indian/Alaska Native (AI/AN) communities in prevention and treatment of COVID-19, including vaccine uptake. Thirteen Community Health Representatives (CHRs) from three Arizona Native nations tailored education materials to each community. CHRs delivered the intervention to over 160 community members and administered a pre-posttest to assess trusted sources of information, knowledge, and self-efficacy and intention regarding COVID-19 vaccines. Based on pre-posttest results, doctors/healthcare providers and CHRs were the most trusted health messengers for COVID-19 information; contacts on social media, the state and federal governments, and mainstream news were among the least trusted. Almost two-thirds of respondents felt the education session was relevant to their community and culture, and more than half reported using the education materials to talk to a family member or friend about getting vaccinated. About 67% trusted the COVID-19 information provided and 74% trusted the CHR providing the information. Culturally and locally relevant COVID-19 vaccine information was welcomed and used by community members to advocate for vaccination. The materials and education provided by CHRs were viewed as helpful and emphasized the trust and influence CHRs have in their communities.

Cervical cancer is the 4th most common type of cancer in women world-wide. Many factors play a role in cervical cancer development/progression that include genetics, social behaviors, social determinants of health, and even the microbiome. The prevalence of HPV infections and cervical cancer is high and often understudied among Native American communities. While effective HPV vaccines exist, less than 60% of 13- to 17-year-olds in the general population are up to date on their HPV vaccination as of 2020. Vaccination rates are higher among Native American adolescents, approximately 85% for females and 60% for males in the same age group. Unfortunately, the burden of cervical cancer remains high in many Native American populations. In this paper, we will discuss HPV infection, vaccination and the cervicovaginal microbiome with a Native American perspective. We will also provide insight into new strategies for developing novel methods and therapeutics to prevent HPV infections and limit HPV persistence and progression to cervical cancer in all populations.

Income, education, job security, food and housing, and gender and race are all examples of the social determinants of health. These factors influence the health and well-being of patients, as well as how they interact with health care providers and receive health care, and unfortunately, certain biases can become a barrier to maintaining good health in some communities. Indigenous groups in North America and US-associated Pacific jurisdictions have been subjected to occupation and forced relocation, mandated boarding schools, and other attempts by state and federal governments to eliminate their cultural strengths and resources. Indigenous Public Health illustrates how successful community engagement strategies, programs, and resources within Indigenous communities have resulted in diverse, successful public health programs, and helped community members overcome barriers to health. Editors Linda Burhansstipanov and Kathryn L. Braun explore the problems that impact engagement efforts, discuss public health topics, acknowledge and honor the strengths of different communities, and emphasize that collaboration and the sharing of resources can only improve lives.

Self-assembling proteins commonly occur in nature and have been shown to have potential as a vaccine platform with displayed peptide antigens. Beta-strand peptides that alternate hydrophobic and hydrophilic amino acids self-assemble into a beta-sheet bilayer. This format may cause an immunogenic response with an antigen and therefore be an effective vaccine for HPV. Current HPV vaccines are virus-like particles which are not as robust or as easily stored as the peptides. In addition, current HPV vaccines do not protect against all types of HPV. The goal is to create Q11 (Ac-QQKFQFQFEQQ-NH2) and KFE8 (Ac-FKFEFKFE-NH2) peptide sequences alongside HPV L2 protein sequences. We hypothesize that these peptides will cause an immune system response with B cells. Standard Fmoc solid phase peptide synthesis was utilized to synthesize all peptides. Preliminary animal models to test immunogenicity and effectiveness of the vaccine was completed. Data consists of peptide synthesis, HPLC purification, MALDI-TOF and CD spectroscopy, TEM imaging, and ELISA assays. TEM results showed fibril formation with HPV antigen and ELISA results have shown the potential of this peptide platform, but further studies are needed. In conclusion, self-assembling peptides with multivalent display of antigens could be an efficient way to make next generation HPV vaccines with potential for developing vaccines for other diseases as well.

Native Americans are the least represented population in science fields. In recent years, undergraduate and graduate level summer research programs that aimed to increase the number of Native Americans in science have made some progress. As new programs are designed, key characteristics that address science self-efficacy and science identity and provide supports for Native American students’ commitment to a scientific career should be considered. In this study, we used sequential mixed methods to investigate the potential of culturally tailored internship programs on Native American persistence in science. We analyzed surveys and interviews with Native American students to understand their perceptions of themselves in relation to science research and how summer research experiences might develop science identities. Based on regression modeling, science identity, but not science self-efficacy, predicted intent to persist in science. In turn, science self-efficacy and Native American identity predicted science identity, and this suggests cultural identity is central to Native American persistence in science. In interviews, students’ comments reinforced these findings and shed light on students’ reasoning about the kinds of science experiences they sought; specifically, they chose to participate in culturally tailored internships because these programs provided a sense of belonging to the scientific community that did not conflict with their cultural identities. Based on our analysis, we propose an Indigenous science internship model and recommend that agencies target funding for culturally tailored programs from high school through early-investigator levels as well as provide inclusive programmatic and mentoring guidelines.

Historically excluded students (underrepresented minorities, females, low income, disabled, etc.) pursuing college degrees are faced with unique challenges that often result in them leaving science, technology, engineering, math (STEM), and health science fields. The goal of the Chemistry and Culture Workbook is to engage students from diverse backgrounds and encourage a sense of belonging within the STEM and health science fields. Native American culture and stories are emphasized but instructors can modify to include examples from their student demographics, note: examples will be provided with the instructor manual. Curriculum includes the work from two Native American chemists: Dr. Naomi Lee who is Onodowaga (Seneca) and Dr. Joslynn Lee who is of Diné (Navajo), K’awaika (Laguna Pueblo) and Haak’u (Acoma Pueblo).

Despite a global and nationwide decrease, Native Americans continue to experience high rates of cancer morbidity and mortality. Vaccination is one approach to decrease cancer incidence such as the case of cervical cancer. However, the availability of vaccines does not guarantee uptake, as evident in the Coronavirus 2019 pandemic. Therefore, as we consider current and future cancer vaccines, there are certain considerations to be mindful of to increase uptake among Native Americans such as the incidence of disease, social determinants of health, vaccine hesitancy, and historical exclusion in clinical trials. This paper primarily focuses on human papillomavirus (HPV) and potential vaccines for Native Americans. However, we also aim to inform researchers on factors that influence Native American choices surrounding vaccination and interventions including cancer therapies. We begin by providing an overview of the historical distrust and trauma Native Americans experience, both past and present. In addition, we offer guidance and considerations when engaging with sovereign Tribal Nations in vaccine development and clinical trials in order to increase trust and encourage vaccine uptake.

Amphipathic peptides with amino acids arranged in alternating patterns of hydrophobic and hydrophilic residues efficiently self-assemble into β-sheet bilayer nanoribbons. Hydrophobic side chain functionality is effectively buried in the interior of the putative bilayer of these nanoribbons. This study investigates consequences on self-assembly of increasing the surface area of aromatic side chain groups that reside in the hydrophobic core of nanoribbons derived from Ac-(XKXE)2-NH2 peptides (X = hydrophobic residue). A series of Ac-(XKXE)2-NH2 peptides incorporating aromatic amino acids of increasing molecular volume and steric profile (X = phenylalanine [Phe], homophenylalanine [Hph], tryptophan [Trp], 1-naphthylalanine [1-Nal], 2-naphthylalanine [2-Nal], or biphenylalanine [Bip]) were assessed to determine substitution effects on self-assembly propensity and on morphology of the resulting nanoribbon structures. Additional studies were conducted to determine the effects of incorporating amino acids of differing steric profile in the hydrophobic core (Ac-X1KFEFKFE-NH2 and Ac-(X1,5KFE)-NH2 peptides, X = Trp or Bip). Spectroscopic analysis by circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopy indicated β-sheet formation for all variants. Self-assembly rate increased with peptide hydrophobicity; increased molecular volume of the hydrophobic side chain groups did not appear to induce kinetic penalties on self-assembly rates. Transmission electron microscopy (TEM) imaging indicated variation in fibril morphology as a function of amino acid in the X positions. This study confirms that hydrophobicity of amphipathic Ac-(XKXE)2-NH2 peptides correlates to self-assembly propensity and that the hydrophobic core of the resulting nanoribbon bilayers has a significant capacity to accommodate sterically demanding functional groups. These findings provide insight that may be used to guide the exploitation of self-assembled amphipathic peptides as functional biomaterials.

American Indian and Alaska Native women had approximately twice the incidence of cervical cancer as white women. Preventive measures for cervical cancer relyon screening and HPV vaccination. However, vaccine series completionand catch-up vaccinations for eligible adults are lowacross all racial/ethnic groups. Therefore, the aim of this study was to identify gaps in knowledge and evaluate the attitudes toward HPV and the vaccine among AIANswith various levels of training in the STEM and health-relatedfields.A surveywas used to collect data from audience members at two national conferences geared towards American Indian and Alaska Nativesin health and STEM fieldsin September 2017. Avignette study was administered via a live electronic poll to test knowledge (true/false questions), attitudes,and to collect demographic information. Respondents self-identified as primarily American Indian and Alaska Native (74%), pursuing or completed a graduate degree (67%), and female (85%). Most respondents (86%) were aware of HPV-associated cancer in men. However, most (48-90%) answered incorrectly to detailed true/false statements about HPV and available vaccines. After educational information was provided, opinions collected via vignettes highlighted mainly positive attitudes toward vaccination; specifically, that vaccines are safe and all eligible community members should be vaccinated (75% and 84%,respectively). We observed that our respondents with higher educational attainment still lacked accurate knowledge pertaining to HPV and the vaccine. Overall, continued education about HPV and the vaccine is needed across all levels of education including American Indian and Alaska Native community members and health professionals.

Globally, cervical cancer is among the leading malignancies in women, with virtually all cases caused by the human papillomavirus (HPV). In the United States, approximately 13200 cases of cervical cancer are diagnosed each year, and annual mortality exceeds 4000. Thus far, 14 genotypes (HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) have been identified as oncogenic or “high-risk” HPV (hrHPV), with HPV-16 and 18 causing 70% of reported cervical malignancies worldwide. The remaining 30% of cervical cancer cases result from infections with other hrHPV genotypes. From 1999 to 2009, American Indian women had twice the incidence of cervical cancer and twice the associated mortality rate as white women. In the Northern Plains service region of the Indian Health Service (Montana, Wyoming, North Dakota, South Dakota, Nebraska, Iowa, Minnesota, Wisconsin, Michigan, Illinois, and Indiana), cervical cancer incidence among American Indian women was twice that of white women in the same region, while associated mortality rates were 4 times higher. The cervical cancer disparity is primarily attributed to a lack of screening and unequal access to health care. However, other factors may contribute, such as a higher prevalence of hrHPV among American Indians. ... No study has sampled a sufficient number of American Indian women across the United States to enable estimates of past or present hrHPV prevalence or vaccination impact in this population. However, tribe-specific hrHPV prevalence was estimated in certain American Indian communities. A clinic-based study of 287 American Indian women in South Dakota conducted before widespread uptake of vaccination found an HPV prevalence of 14.3% for oncogenic genotypes and 7.0% for nononcogenic types. In another clinic-based study in South Dakota, our research group reported an hrHPV prevalence of 30% in a sample of 235 American Indian women, compared to 16% among 246 white women. Our group also recruited a convenience sample of 329 American Indian women residing on the Hopi Reservation in Arizona who submitted home-based self-collected vaginal swabs; we reported a combined prevalence of 22% for 14 hrHPV genotypes. In that sample, hrHPV prevalence declined with age, from 38% in women aged 21–24 years to 14% in women aged 50 years and older. The hrHPV prevalence variation among American Indian women were attributed to population-specific differences in lifestyle and behavioral risk factors, such as limited education, limited HPV knowledge, more sexual partners, younger age at sexual debut, and younger age at first pregnancy. Therefore, our objective was to report the findings from the largest study of hrHPV prevalence in American Indian women (n = 698) conducted to date. Finally, because American Indian and Alaskan Native women are insufficiently sampled in national studies, we estimated the potential impact of universal vaccination in this population by evaluating the prevalence for hrHPV types relative to age for 4vHPV and 9vHPV vaccines. Future analyses will evaluate the lifestyle and behavioral risk factors for hrHPV infection from this convenience sample of American Indian women.

Literature shows that students who enter the science, technology, engineering, mathematics, and medical-related (STEMM) pipeline at earlier stages of their career are more likely to be successful. This is especially true for under-represented and economically disadvantaged students. Despite the increasing number of students entering the pipeline, American Indian and Alaska Native (AIAN) students still have a higher attrition rate compared to other ethnic groups. Educators and government agencies have worked to improve the success rate for AIAN students across all levels and fields by developing various programs aimed at training and mentorship. In 2007, the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) in Bethesda, MD, increased their outreach efforts for recruiting AIAN students for the summer internship program. Our goal was to develop a culturally tailored research-training program that could recruit and retain AIAN students into STEMM degrees and careers. We adapted an existing program that provides training in biomedical science and mentorship at an NINDS research laboratory. From 2007 to 2016, of the 41 AIAN interns who participated, 35 (85%) remained in STEMM fields. Five interns obtained post baccalaureate positions at NIH and four entered graduate or medical school. These successful outcomes were brought about only after navigating myriad obstacles. We identified obstacles for AIAN student participation, and made adaptations to the summer internship. We made design decisions regarding recruitment, feasibility, lab placement and mentorship, supporting research and social networking, and sustaining AIAN culture. This design case highlights the obstacles and strategies for success that we developed.

Human herpesvirus-6 (HHV-6) is a ubiquitous virus with the human adult population being greater than 90% seropositive. Primary infections occur by the age of two years and result in the childhood disease, roseola infantum. Infected individuals retain a persistent lifelong infection but typically remain asymptomatic. However, HHV-6 has been associated with certain neurological disorders such as multiple sclerosis (MS). Antiviral therapies against human herpesviruses include a variety of targets such as reverse transcriptase and integrase inhibitors; the enzymes required for viral genome replication and integration, respectively. Due to functional similarities between the human herpesviruses, certain approved therapies are being investigated for treatment against HHV-6 in MS patients. However, antiviral therapies specific for HHV-6 do not exist nor does a effective treatment for MS. Therefore, our goal is to further investigate the potential antiviral properties of cyclopropavir derivative, MBX-400, against HHV-6. Zemlicka et al. synthesized numerous cyclopropavir derivatives and showed potential antiviral activity as nucleoside-based DNA polymerase inhibitors against human herpesviruses. We investigated the antiviral activity of the 2,2-bis-hydroxymethyl-cyclopropavir derivative, MBX-400, using our HHV-6 in vitro protocol. Infections were established with SUPT-1T-cell lines for HHV-6A (strain U1101) and HHV-6B (strain Z29) variants, respectively. Proviral loads were detected with real-time Taqman PCR. Preliminary findings showed antiviral activity against HHV-6B at a concentration of 20 μM for MBX-400. The control (DMSO) exhibited the expected trend in viral growth over a period of seven days for both the supernatant and cell lysate. However, MBX-400 indicated an inhibitory effect, approximately 10-fold less, than the control for both the supernatant and cell lysate. A concentration dependent inhibitory effect was also observed for serial dilutions (1:10) of MBX-400. Lastly, infected cells were left untreated for three days, upon addition of drug at 20.0 μM, the proviral load plateaued throughout the remaining seven-day period. Therefore, it is acknowledged that treatment of HHV-6B SUPT-1 infected cells with 20.0 μM of 2,2-bis-hydroxymethyl-cyclopropavir, MBX-400, inhibited proviral load for both the supernatant and cell lysate. Further studies are being conducted using the same model with HHV-6A. The sponsoring organization is Viral Immunology Section, NINDS/NIH, Bethesda, Maryland, United States.

Amphipathic peptides have an increased propensity to self-assemble into amyloid-like β-sheet fibrils when their primary sequence pattern consists of alternating hydrophobic and hydrophilic amino acids. These fibrils adopt a bilayer architecture composed of two β-sheets laminated to bury the hydrophobic side chains of the β-sheet in the bilayer interior, leaving the hydrophilic side chains exposed at the bilayer surface. In this study, the effects of altering the sequence pattern of amphipathic peptides from strictly alternating hydrophobic/hydrophilic repeats to more complex patterning of hydrophobic and hydrophilic residues on self-assembly of the resulting sequences is reported. Self-assembly of the Ac-(FKFE)2-NH2 peptide was compared to that of four related sequences with varied amino acid sequence patterning: Ac-(FK)2(FE)2-NH2, Ac-KEFFFFKE-NH2, Ac-(KFFE)2-NH2, and Ac-FFKEKEFF-NH2. The Ac-(FKFE)2-NH2 and Ac-(FK)2(FE)2-NH2 peptides effectively self-assembled at high (1.0 mM) and low (0.2 mM) concentrations (pH 3–4) into β-sheet nanoribbons that were 8 and 4 nm wide, respectively. The Ac-KEFFFFKE-NH2 peptide failed to self-assemble at low concentration (pH 3–4), but self-assembled into distinct nanotapes that were ∼20 nm in width at high concentration. Ac-(KFFE)2-NH2 and Ac-FFKEKEFF-NH2 failed to self-assemble into fibril/tape-like materials at either high or low concentration at pH 3–4, although Ac-FFKEKEFF-NH2 formed micelle-like aggregates at higher concentrations. At neutral pH, similar self-assembly behavior was observed for each peptide as was observed at acidic pH. An exception was the Ac-FFKEKEFF-NH2 peptide, which formed ∼20 nm nanotapes at neutral pH. These results indicate that amino acid sequence patterns exert a profound influence on self-assembly propensity and morphology of the resulting materials even when the overall hydrophobicity or charge of the related peptides are identical. Sequence pattern variation can thus be exploited as a variable in the creation of novel materials composed of self-assembled peptides.

Amphipathic peptides composed of alternating hydrophobic and hydrophilic amino acids are a privileged class of peptide, which have a high propensity to self-assemble into β-sheet fibrils. The Ac-(FKFE)2-NH2 peptide has been extensively studied and forms putative β-sheet bilayer fibrils in which the hydrophobic Phe side chains are organized to a single face of each constituent sheet; upon bilayer formation, these hydrophobic benzyl groups are sequestered in the hydrophobic core of the resulting fibril. In order for the Phe side chains to be uniformly displayed on one face of Ac-(FKFE)2-NH2 β-sheets, an antiparallel packing orientation in which one amino acid residue is unpaired must be adopted. Based on molecular models, we hypothesized that truncated seven amino acid derivatives of Ac-(FKFE)2-NH2 in which either the N-terminal Phe residue (Ac-KFEFKFE-NH2) or the C-terminal Glu residue (Ac-FKFEFKF-NH2) is eliminated should readily self-assemble into β-sheet bilayers in which all hydrogen bond and hydrophobic/charge interactions are satisfied. We found, however, that these minute changes in peptide sequence have unanticipated and dramatic effects on the self-assembly of each peptide. Ac-FKFEFKF-NH2 self-assembled into fibrils with unique morphology relative to the parent peptide, whereas the Ac-KFEFKFE-NH2 peptide had a strongly reduced propensity to self-assemble, even failing to self-assemble altogether under some conditions. These findings provide significant insight into the effect of sequence length and strand registry as well as hydrophobicity and charge on the self-assembly of simple amphipathic peptides to illuminate the possibility of tuning self-assembly processes and the resulting structures with minute changes to peptide sequence.

Viral infections have been associated with autoimmune diseases such as multiple sclerosis (MS), but the exact mechanisms how viral infection could induce autoimmunity are poorly characterized. Although molecular mimicry have been suggested as a mechanism, convincing viral and autoantigen targets have not been identified in MS. Another possibility is that viral infection could induce and/or modify cellular proteins that are recognized by the immune system. Human herpesvirus 6 (HHV-6) antigen and nucleic acids have been found in MS brain lesions suggesting that HHV-6 might participate to the lesion development. To identify possible intrathecal humoral immune response targets in human HHV-6 infected cells we used immunoprecipitation based mass spectrometry analysis to identify possible cellular targets present only in HHV-6 infected cells. Furthermore, we identified MS brain endogenous IgG protein targets using similar approach. Cerebrospinal fluid (CSF) IgG pulled 26 unique proteins from infected cells that did not came up with serum or from non-infected cells. Three of these proteins were identified as MS brain lesion associated endogenous IgG targets as well. We are in the process of validating these results with other immunoassays. Our results suggest that HHV-6 infection can induce cellular proteins that are recognized by MS CSF IgG, and thus, might provide targets for the autoimmunity in MS.