COVID-19 InfoVaccines: A WHO-supported educational project to promote COVID-19 vaccination information among professionals and the general population.

COVID-19 vaccine uptake varied across countries, in part due to vaccine hesitancy fueled by a lack of trustworthy information. To help health workers provide evidence-based answers to common questions about COVID-19 vaccines and vaccination, and thereby, assist individuals´ decisions on vaccine acceptance, COVID-19 InfoVaccines, a joint WHO-EU project, was launched in February 2021 to support COVID-19 vaccine rollout in 6 Eastern European countries. COVID-19 InfoVaccines was made available in seven languages and shared on social media networks. A total of 262,592 users accessed COVID-19 InfoVaccines.com between February 11, 2021, and January 31st, 2023. The users were most interested in: general questions; vaccine efficacy and duration of protection; vaccine safety; vaccine co-administration, and dose-interval and interchangeability; though the interest in a specific theme varied in function of the epidemiological situation. A total of 118,510 (45.1%) and 46,644 (17.7%) users scrolled up to 35% and 75% of the COVID-19 InfoVaccines webpage, respectively. The average engagement rate was 71.61%. The users accessed COVID-19 InfoVaccines from 231 countries and territories, but the majority were in Ukraine (N = 38,404; 14.6%), Spain (N = 23,327; 8.9%), and Argentina (N = 21,167; 8.1%). Older Facebook users were more interested in COVID-19 information than younger individuals (X2 p-value < .0001). Two hundred twenty-eight videos were shared on YouTube. The average Click-Through-Rate on Facebook was 7.82%, and that on YouTube was 4.4%, with 60 videos having a Click-Through-Rate >5%, falling in the range of average YouTube video Click-Through-Rate (2% - 10%). As misinformation about vaccines and vaccination spreads easily and can negatively impact health-related decisions, initiatives like COVID-19 InfoVaccines are crucial to facilitate access to reliable information.

Enhancement of Biodiesel Production via Ultrasound Technology: A Mathematical Study.

Biodiesel is one of the alternative renewable energy sources that has received a lot of attention since it is clean, green energy. Different sources can be used for the production of biodiesel, but the most appropriate and economical method relies on the transesterification of methanol with the nonedible vegetable oil from the fruit of the Jatropha curcas plant. Molar ratio, vessel diameter, catalyst concentration, and ultrasound all have a substantial influence on the synthesis of biodiesel by the transesterification process. Among these factors, the diameter of the vessel and the ultrasonic effect through mass transfer limitations have a significant impact on successful reaction completion. In this research work, we have developed a mathematical model to analyze the three-step transesterification process and side saponification reaction in the presence of a potassium hydroxide catalyst. The model considers the influence of mixing intensity variations, including ultrasound, on the mass transfer in different phases. The mass transfer rate is calculated using the modified Dittus-Boelter correlation. An optimal control approach through the minimum principle by Pontryagin is applied to maximize the production of biodiesel at minimal cost. The novelty of this research, which we have derived from our analytical as well as numerical results, considering industrial processes, is that more than 97% biodiesel yield conversion is to be obtained at 50 kHz ultrasound frequency, a 6:1 methanol-to-Jatropha-oil molar ratio, and 1 m of vessel diameter within 50 min using optimal control theory.

Essential functions of Inositol hexakisphosphate (IP6) in Murine Leukemia Virus replication.

We have investigated the function of inositol hexakisphosphate (IP6) and inositol pentakisphosphate (IP5) in the replication of murine leukemia virus (MLV). While IP6 is known to be critical for the life cycle of HIV-1, its significance in MLV remains unexplored. We find that IP6 is indeed important for MLV replication. It significantly enhances endogenous reverse transcription (ERT) in MLV. Additionally, a pelleting-based assay reveals that IP6 can stabilize MLV cores, thereby facilitating ERT. We find that IP5 and IP6 are packaged in MLV particles. However, unlike HIV-1, MLV depends upon the presence of IP6 and IP5 in target cells for successful infection. This IP6/5 requirement for infection is reflected in impaired reverse transcription observed in IP6/5-deficient cell lines. In summary, our findings demonstrate the importance of capsid stabilization by IP6/5 in the replication of diverse retroviruses; we suggest possible reasons for the differences from HIV-1 that we observed in MLV.

Evaluating the hepatitis B vaccination impact in the Republic of Moldova: A nationwide representative serosurvey of children born in 2013.

Objectives: The WHO European Region set targets for the control of hepatitis B through immunization, including prevalence of hepatitis B surface antigen (HBsAg) at ≤0.5% in vaccinated cohorts. The Republic of Moldova implemented universal hepatitis B vaccination since 1995. We conducted a nationwide representative serosurvey to estimate HBsAg seroprevalence in children born in 2013 to validate hepatitis B control targets. Methods: We used probability-based sampling and a two-stage cluster design. All children born in 2013 and registered in primary healthcare facilities were eligible for participation. We tested blood samples of all participants for hepatitis B core antibody (anti-HBc), using Enzyme-Linked Immunosorbent Assay (ELISA). Anti-HBc-positive samples were tested for HBsAg and HBsAg-positive samples confirmed, using ELISA. We obtained information on hepatitis B vaccination from vaccination cards. Results: Of 3352 sampled children, 3064 (91%) participated. Most participating children were 7 years old (n = 3030, 99%), 1426 (48%) were girls. The weighted, national seroprevalence estimate was 3.1% (95% confidence interval = 2.1-4.5) for anti-HBc and 0.21% (95% confidence interval = 0.08-0.53) for HBsAg. Conclusion: The study demonstrated the impact of hepatitis B vaccination and allowed the Republic of Moldova to validate regional hepatitis B control targets. Other countries with high vaccination coverage could use hepatitis B serosurveys and apply for validation. Sustained efforts in the Republic of Moldova will be crucial on the path to hepatitis B elimination.

Administration of the glutamate-modulating drug, riluzole, after stress prevents its delayed effects on the amygdala in male rats.

Extracellular glutamate levels are elevated across brain regions immediately after stress. Despite sharing common features in their genesis, the patterns of stress-induced plasticity that eventually take shape are strikingly different between these brain areas. While stress causes structural and functional deficits in the hippocampus, it has the opposite effect on the amygdala. Riluzole, an FDA-approved drug known to modulate glutamate release and facilitate glutamate clearance, prevents stress-induced deficits in the hippocampus. But whether the same drug is also effective in countering the opposite effects of stress in the amygdala remains unexplored. We addressed this question by using a rat model wherein even a single 2-h acute immobilization stress causes a delayed expression of anxiety-like behavior, 10 days later, alongside stronger excitatory synaptic connectivity in the basolateral amygdala (BLA). This temporal profile-several days separating the acute stressor and its delayed impact-allowed us to test if these effects can be prevented by administering riluzole in drinking water after acute stress. Poststress riluzole not only prevented the delayed increase in anxiety-like behavior on the elevated plus maze but also blocked the increase in spine density on BLA neurons 10 days later. Further, stress-induced increase in the frequency of miniature excitatory postsynaptic currents recorded in BLA slices, 10 days later, was also blocked by the same poststress riluzole administration. Together, these findings underscore the importance of therapeutic strategies, aimed at glutamate uptake and modulation, in correcting the delayed behavioral, physiological, and morphological effects of stress on the amygdala.

Addressing Determinants of Immunization Inequities Requires Objective Tools to Devise Local Solutions.

Universal immunization substantially reduces morbidity and mortality from vaccine-preventable diseases. In recent years, routine immunization coverage has varied considerably among countries across the WHO European Region, and among different populations and districts within countries. It has even declined in some countries. Sub-optimal immunization coverage contributes to accumulations of susceptible individuals and can lead to outbreaks of vaccine-preventable diseases. The European Immunization Agenda 2030 (EIA2030) seeks to build better health in the WHO European Region by ensuring equity in immunization and supporting immunization stakeholders in devising local solutions to local challenges. The factors that influence routine immunization uptake are context specific and multifactorial; addressing immunization inequities will require overcoming or removing barriers to vaccination for underserved individuals or populations. Local level immunization stakeholders must first identify the underlying causes of inequities, and based on this information, tailor resources, or service provision to the local context, as per the organization and characteristics of the health care system in their countries. To do this, in addition to using the tools already available to broadly identify immunization inequities at the national and regional levels, they will need new pragmatic guidance and tools to address the identified local challenges. It is time to develop the necessary guidance and tools and support immunization stakeholders at all levels, especially those at the subnational or local health centre levels, to make the vision of EIA2030 a reality.

Developing COVID-19 vaccine recommendations during the pandemic: The experience of Serbia's Expert Committee on Immunization.

A National Immunization Technical Advisory Group (NITAG) is a multi-disciplinary body of national experts that provide evidence-based recommendations to policy-makers to assist them in making informed immunization policy and programme decisions. During the COVID-19 pandemic, NITAGs faced many challenges in making evidence-based recommendations for COVID-19 vaccines due to the rapidly evolving situation with new vaccine products available in a short time period and limited data on vaccine effectiveness. The authors reviewed the process used by Serbia's NITAG, which is called the Serbian Expert Committee on Immunization, to develop COVID-19 vaccine recommendations during the pandemic. The article examines the challenges and successes faced by the committee. Serbia's expert committee used the best available evidence to develop over forty recommendations on all aspects of COVID-19 vaccination. These expert committee recommendations facilitated the early procurement and successful roll-out of COVID-19 vaccines, guidance for vaccination of individuals at the highest risk, and high COVID-19 vaccination coverage in the country. The availability of five COVID-19 vaccines in Serbia was an advantage for the successful roll-out but posed challenges for the expert committee. Serbia's expert committee plans to use the experience and best practices developed during the pandemic to improve and expand its work moving forward.

COVID-19 vaccination roll-outs in eleven small countries within the WHO European region; Lessons learned.

The development and administration of COVID-19 vaccines has been an essential element in controlling the COVID-19 pandemic. However, countries worldwide have faced challenges in planning and implementing vaccination strategies. The aim of the current paper is to describe the situation faced by small countries in the WHO European Region in implementing their national vaccination strategies during the first stages of the planned roll-out (up to May 2021). This paper uses information from the WHO Small Countries Initiative (SCI), which includes a network of 11 countries with populations of ≤ 2 million (Andorra, Cyprus, Estonia, Iceland, Latvia, Luxembourg, Malta, Monaco, Montenegro, San Marino, and Slovenia). The SCI countries faced many challenges including: a lack of appropriate vaccination centers, adequate workforce, and registration/booking systems to cope with the unprecedented vaccine storage and administration demands; difficulties for high-risk groups (e.g., older individuals and those with health problems or cognitive impairment) to access vaccination sites or use digital registration/booking systems; vaccine wastage due to canceled appointments; and inequalities in vaccine uptake. Innovative programmatic interventions were implemented to facilitate the vaccination uptake of the populations such as: the creation of non-medical vaccination sites and mobile vaccination units; on-site vaccination of people in long-term residential facilities and long-term medical wards; diversifying health workforce like redeployment of healthcare professionals and use of medical students and retired medical professionals; campaigns with clear information to the general public (in multiple languages where necessary) both offline and online; use of digital registration/booking systems and alternative (non-digital) registration/booking systems for relevant individuals; and administration of excess vaccine doses to non-priority groups to avoid wastage.

Cholesterol Binds the Amphipathic Helix of IFITM3 and Regulates Antiviral Activity.

The interferon-induced transmembrane (IFITM) proteins broadly inhibit the entry of diverse pathogenic viruses, including Influenza A virus (IAV), Zika virus, HIV-1, and SARS coronaviruses by inhibiting virus-cell membrane fusion. IFITM3 was previously shown to disrupt cholesterol trafficking, but the functional relationship between IFITM3 and cholesterol remains unclear. We previously showed that inhibition of IAV entry by IFITM3 is associated with its ability to promote cellular membrane rigidity, and these activities are functionally linked by a shared requirement for the amphipathic helix (AH) found in the intramembrane domain (IMD) of IFITM3. Furthermore, it has been shown that the AH of IFITM3 alters lipid membranes in vitro in a cholesterol-dependent manner. Therefore, we aimed to elucidate the relationship between IFITM3 and cholesterol in more detail. Using a fluorescence-based in vitro binding assay, we found that a peptide derived from the AH of IFITM3 directly interacted with the cholesterol analog, NBD-cholesterol, while other regions of the IFITM3 IMD did not, and native cholesterol competed with this interaction. In addition, recombinant full-length IFITM3 protein also exhibited NBD-cholesterol binding activity. Importantly, previously characterized mutations within the AH of IFITM3 that strongly inhibit antiviral function (F63Q and F67Q) disrupted AH structure in solution, inhibited cholesterol binding in vitro, and restricted bilayer insertion in silico. Our data suggest that direct interactions with cholesterol may contribute to the inhibition of membrane fusion pore formation by IFITM3. These findings may facilitate the design of therapeutic peptides for use in broad-spectrum antiviral therapy.

Riluzole prevents stress-induced spine plasticity in the hippocampus but mimics it in the amygdala.

Stress elicits divergent patterns of structural plasticity in the amygdala and hippocampus. Despite these contrasting effects, at least one of the immediate consequences of stress - elevated levels of extracellular glutamate - is similar in both brain areas. This raises the possibility that the contrasting effects of stress on neuronal plasticity is shaped by differences in astrocytic glutamate clearance in these two brain areas. Although astrocytes play a key role in glutamate reuptake, past analyses of, and interventions against, stress-induced plasticity have focused largely on neurons. Hence, we tested the impact of riluzole, which potentiates glutamate clearance by astrocytic glutamate transporters, on principal neurons and astrocytes in the basal amygdala (BA) and hippocampal area CA1. Chronic immobilization stress reduced spine-density on CA1 pyramidal neurons of male rats. Riluzole, administered in the drinking water during chronic stress, prevented this decrease; but, the drug by itself had no effect. In contrast, the same chronic stress enhanced spine-density on BA principal neurons, and this effect, unlike area CA1, was not reversed by riluzole. Strikingly, riluzole treatment alone also caused spinogenesis in the BA. Thus, the same riluzole treatment that prevented the effect of stress on spines in the hippocampus, mimicked its effect in the amygdala. Further, chronic stress and riluzole alone decreased the neuropil volume occupied by astrocytes in both the BA and CA1 area. Riluzole treatment in stressed animals, however, did not reverse or further add to this reduction in either region. Thus, while the effects on astrocytes were similar, neuronal changes were distinct between the two areas following stress, riluzole and the two together. Therefore, similar to the impact of repeated stress, pharmacological potentiation of glutamate clearance, with or without stress, also leads to differential effects on dendritic spines in principal neurons of the amygdala and hippocampus. This highlights differences in the astrocytic glutamate reuptake machinery that are likely to have important functional consequences for stress-induced dysfunction, and its reversal, in two brain areas implicated in stress-related psychiatric disorders.

Diphtheria in the WHO European Region, 2010 to 2019.

BackgroundDiphtheria is uncommon in the World Health Organization (WHO) European Region. Nevertheless, sporadic cases, sometimes fatal, continue to be reported.AimTo report on diphtheria cases and coverage with first and third doses of diphtheria, tetanus and pertussis vaccines (DTP1 and DTP3, respectively) for 2010-19 in the Region with a focus on 2019.MethodsData on diphtheria cases were obtained from WHO/United Nations International Children's Emergency Fund (UNICEF) Joint Reporting Forms submitted annually by the Region's Member States. WHO/UNICEF Estimates of National Immunization Coverage for DTP1 and DTP3 were summarised for 2010-19. For 2019, we analysed data on age, and vaccination status and present data by country on DTP1 and DTP3 coverage and the percentage of districts with ≥ 90% and < 80% DTP3 coverage.ResultsFor 2010-19, 451 diphtheria cases were reported in the Region. DTP1 and DTP3 coverage was 92-96% and 95-97%, respectively. For 2019, 52 cases were reported by 11 of 48 countries that submitted reports (including zero reporting). Thirty-nine countries submitted data on percentage of their districts with ≥ 90% and < 80% DTP3 coverage; 26 had ≥ 90% districts with ≥ 90% coverage while 11 had 1-40% districts with < 80% coverage.ConclusionLong-standing high DTP3 coverage at Regional level probably explains the relatively few diphtheria cases reported in the Region. Suboptimal surveillance systems and inadequate laboratory diagnostic capacity may also be contributing factors. Still, the observed cases are of concern. Attaining high DTP3 coverage in all districts and implementing recommended booster doses are necessary to control diphtheria and prevent outbreaks.

Evaluation strategies for measuring pneumococcal conjugate vaccine impact in low-resource settings.

OBJECTIVES: Pneumococcal conjugate vaccines (PCVs) are effective in reducing pneumococcal disease. We measured 13-valent PCV (PCV13) effect on different pneumococcal outcomes using diverse studies in Lao People's Democratic Republic. METHODS: Studies included: pre-PCV13 population-based record review of hospitalized childhood pneumonia cases; acute respiratory infection (ARI) study post-PCV13 to demonstrate effectiveness (VE) against hypoxic pneumonia; invasive pneumococcal disease (IPD) surveillance in all ages (2004-2018); carriage studies in children hospitalized with ARI (2013-2019); community carriage surveys pre- and post-PCV13. RESULTS: Annual pneumonia incidence rate in children pre-PCV13 was 1,530 (95% confidence interval [CI] 1,477-1,584) per 100,000. Adjusted VE against hypoxic pneumonia was 37% (95% CI 6-57%). For IPD, 85% (11/13) of cases were due to vaccine-types pre-PCV13, and 43% (3/7) post-PCV13 in children aged <5 years; for ≥5 years, 61% (27/44) and 42% (17/40), respectively. For ARI cases, adjusted VE for vaccine-type carriage was 39% (95% CI 4-60) in <5 year olds; slightly higher than community surveys (23% [95% CI 4-39%] in 12-23 month olds). CONCLUSIONS: Despite limited baseline data, we found evidence of PCV13 impact on disease and carriage. Our approach could be used in similar settings to augment existing WHO PCV evaluation guidelines.

Supporting National Immunization Technical Advisory Groups in the WHO European Region in developing national COVID-19 vaccination recommendations through online communication platform.

National Immunization Technical Advisory Groups are groups of multi-disciplinary experts that provide scientific advice to policy makers to enable them to make informed immunization policy and programme decisions. NITAGs faced challengesusing their routine approach to develop recommendations for COVID-19 vaccines during the pandemic. In response, the WHORegional Office for Europe (Regional Office), with the support of theRobert Koch Institute, developedan innovative approach of a series of webinars, provision of materials, and remote technical assistance to address these challenges. Polls conducted during webinars were used to tailor future webinars and evaluate the effectiveness of these interventions. According to poll results, 76% of participants found the webinars and resources shared very useful in their work on COVID-19 vaccination.The Regional Office plans to build further upon the scope of online communication and establish a regional online platform for NITAGs to further support NITAGs and build capacity.

Progress Toward Hepatitis B Control - World Health Organization European Region, 2016-2019.

In 2019, an estimated 14 million persons in the World Health Organization (WHO) European Region* (EUR) were chronically infected with hepatitis B virus (HBV), and approximately 43,000 of these persons died from complications of chronic HBV infection (1). In 2016, the WHO Regional Office for Europe set hepatitis B control program targets for 2020, including 1) ≥90% coverage with 3 doses of hepatitis B vaccine (HepB3), 2) ≥90% coverage with interventions to prevent mother-to-child transmission (MTCT) of HBV,† and 3) ≤0.5% prevalence of HBV surface antigen (HBsAg)§ in age groups eligible for vaccination with hepatitis B vaccine (HepB) (2-4). This report describes the progress made toward hepatitis B control in EUR during 2016-2019. By December 2019, 50 (94%) of 53 countries in EUR provided routine vaccination with HepB to all infants or children aged 1-12 years (universal HepB), including 23 (43%) countries that offered hepatitis B birth dose (HepB-BD) to all newborns. In addition, 35 (73%) of the 48 countries with universal infant HepB vaccination reached ≥90% HepB3 coverage annually during 2017-2019, and 19 (83%) of the 23 countries with universal birth dose administration achieved ≥90% timely HepB-BD coverage¶ annually during that period. Antenatal hepatitis B screening coverage was ≥90% in 17 (57%) of 30 countries that selectively provided HepB-BD to infants born to mothers with positive HBsAg test results. In January 2020, Italy and the Netherlands became the first counties in EUR to be validated to have achieved the regional hepatitis B control targets. Countries can accelerate progress toward hepatitis B control by improving coverage with HepB and interventions to prevent MTCT and documenting achievement of the HBsAg seroprevalence target through representative serosurveys or, in low-endemicity countries, antenatal screening.

Corticosterone after acute stress prevents the delayed effects on the amygdala.

Even a single 2-hour episode of immobilization stress is known to trigger anxiety-like behavior and increase spine-density in the basolateral amygdala (BLA) of rats 10 days later. This delayed build-up of morphological and behavioral effects offers a stress-free time window of intervention after acute stress, which we used to test a protective role for glucocorticoids against stress. We observed that post-stress corticosterone, given 1 day after acute stress in drinking water, reversed enhanced anxiety-like behavior 10 days later. Quantification of spine-density on Golgi-stained BLA principal neurons showed that the same intervention also prevented the increase in spine numbers in the amygdala, at the same delayed time-point. Further, stress elevated serum corticosterone levels in rats that received vehicle in the drinking water. However, when stress was followed 24 h later by corticosterone in the drinking water, the surge in corticosterone was prevented. Together, these observations suggest that corticosterone, delivered through drinking water even 24 h after acute stress, is capable of reversing the delayed enhancing effects on BLA synaptic connectivity and anxiety-like behavior. Strikingly, although the immobilization-induced surge in corticosterone by itself has delayed detrimental effects on amygdalar structure and function, there exists a window of opportunity even after stress to mitigate its impact with a second surge of exogenously administered corticosterone. This provides a framework in the amygdala for analyzing how the initial physiological and endocrine processes triggered by traumatic stress eventually give rise to debilitating emotional symptoms, as well as the protective effects of glucocorticoids against their development.

Building immunization decision-making capacity within the World Health Organization European Region.

A National Immunization Technical Advisory Group (NITAG) is a multi-disciplinary body of national experts that provides evidence-based recommendations to policy-makers, assisting them in making sound immunization policy and programme decisions. The World Health Organization (WHO) Regional Office for Europe is working to strengthen the capacity of newly-established NITAGs and has targeted efforts on low- and middle-income countries. The Regional Office, in collaboration with WHO Headquarters and USA Centers for Disease Control and Prevention (CDC), developed a new training strategy and held training workshops to improve NITAGs' functioning and ability to make evidence-based recommendations. Feedback from countries that participated in trainings indicated that the updated training materials and interactive approach with follow-up technical support enabled them to align their NITAG charters and processes with WHO recommendations. To ensure continued progress, global and regional partners such as WHO and CDC should continue providing technical support to recently established NITAGs.

Distinct Contributions of Different Domains within the HIV-1 Gag Polyprotein to Specific and Nonspecific Interactions with RNA.

Viral genomic RNA is packaged into virions with high specificity and selectivity. However, in vitro the Gag specificity towards viral RNA is obscured when measured in buffers containing physiological salt. Interestingly, when the binding is challenged by increased salt concentration, the addition of competing RNAs, or introducing mutations to Gag protein, the specificity towards viral RNA becomes detectable. The objective of this work was to examine the contributions of the individual HIV-1 Gag polyprotein domains to nonspecific and specific RNA binding and stability of the initial protein-RNA complexes. Using a panel of Gag proteins with mutations disabling different Gag-Gag or Gag-RNA interfaces, we investigated the distinct contributions of individual domains which distinguish the binding to viral and nonviral RNA by measuring the binding of the proteins to RNAs. We measured the binding affinity in near-physiological salt concentration, and then challenged the binding by increasing the ionic strength to suppress the electrostatic interactions and reveal the contribution of specific Gag-RNA and Gag-Gag interactions. Surprisingly, we observed that Gag dimerization and the highly basic region in the matrix domain contribute significantly to the specificity of viral RNA binding.

Nucleic acid-induced dimerization of HIV-1 Gag protein.

HIV-1 Gag is a highly flexible multidomain protein that forms the protein lattice of the immature HIV-1 virion. In vitro, it reversibly dimerizes, but in the presence of nucleic acids (NAs), it spontaneously assembles into virus-like particles (VLPs). High-resolution structures have revealed intricate details of the interactions of the capsid (CA) domain of Gag and the flanking spacer peptide SP1 that stabilize VLPs, but much less is known about the assembly pathway and the interactions of the highly flexible NA-binding nucleocapsid (NC) domain. Here, using a novel hybrid fluorescence proximity/sedimentation velocity method in combination with calorimetric analyses, we studied initial binding events by monitoring the sizes and conformations of complexes of Gag with very short oligonucleotides. We observed that high-affinity binding of oligonucleotides induces conformational changes in Gag accompanied by the formation of complexes with a 2:1 Gag/NA stoichiometry. This NA-liganded dimerization mode is distinct from the widely studied dimer interface in the CA domain and from protein interactions arising in the SP1 region and may be mediated by protein-protein interactions localized in the NC domain. The formation of the liganded dimer is strongly enthalpically driven, resulting in higher dimerization affinity than the CA-domain dimer. Both detailed energetic and conformational analyses of different Gag constructs revealed modulatory contributions to NA-induced dimerization from both matrix and CA domains. We hypothesize that allosterically controlled self-association represents the first step of VLP assembly and, in concert with scaffolding along the NA, can seed the formation of two-dimensional arrays near the NA.