Virus Acquisition Research Articles

Clinical and Immunologic Outcomes After Immediate or Deferred Antiretroviral Therapy Initiation During Primary Human Immunodeficiency Virus Infection: The Sabes Randomized Clinical Study.

In addition to demonstrated public health benefits on reducing transmission, it remains unclear how early antiretroviral therapy (ART) must be started after acquisition of human immunodeficiency virus (HIV) to maximize individual benefits. We conducted an open-label randomized clinical study in Lima, Peru among adult men who have sex with men and transgender women with acute (HIV-antibody negative/HIV-1 RNA positive) or recent (confirmed negative HIV-antibody or RNA test within 3 months) HIV infection, who were randomized to start ART immediately versus defer by 24 weeks. We evaluated outcomes by treatment arm and immunologic markers by days since estimated date of detectible infection (EDDI). Of 216 participants, 105 were assigned to immediate arm and 111 to deferred arm (median age 26.8 years, 37% with acute HIV). The incidence of non-ART-related adverse events was lower in immediate versus deferred arm (83 vs 123/100 person-years, IRR 0.67 (95% confidence interval [CI] .47, .95; P = .02), the difference dominated by fewer infections in those treated immediately. After 24 weeks of ART, between-group differences in CD4/CD8 cell ratio lessened (P = .09 overall), but differences between those initiating ART ≤ 30 days from EDDI (median 1.03, interquartile range [IQR] 0.84, 1.37), and those initiating > 90 days (0.88, IQR 0.61, 1.11) remained, P = .02. Principal components analysis of 20 immune biomarkers demonstrated distinct patterns between those starting ART > 90 days from EDDI versus those starting within 30 or 90 days (both P < .001). To our knowledge, this is the only evaluation of randomized ART initiation during primary HIV and provides evidence to explicitly consider acute HIV in World Health Organization recommendations for universal ART. NCT01815580.

Insecticide resistance increases the vector competence: a case study in Frankliniella occidentalis

The western flower thrips, Frankliniella occidentalis, is the most efficient vector for Tomato spotted wilt orthotospovirus (TSWV), a devastating plant pathogen. Insecticide resistance is a common issue in pest management. The interactions between insecticide resistance in insect vector and the transmission of plant pathogen, however, are largely unknown. In this study, we assessed the effects of spinosad resistance on TSWV transmission using a pair of near-isogenic lines of susceptible (Ivf03) and resistant (NIL-R) F. occidentalis. NIL-R had a prolonged pre-adult stage, but a shorter adult life span than Ivf03. More importantly, the pupation rate and sex ratio (female/male) in NIL-R were significantly reduced in comparison with Ivf03. When given a shorter acquisition access period (AAP) of 6 h, virus propagation and transmission efficiency in NIL-R were significantly higher than Ivf03. In contrast, a longer AAP of 96 h led to a similar virus acquisition and transmission efficiency for both strains, although TSWV replication was greater in NIL-R. Our combined results suggest that (1) substantial fitness costs (e.g., reduced pupation rate) are associated with spinosad resistance in F. occidentalis; however, (2) insecticide resistance increases vector competence.

Rectal gonorrhoea and chlamydia among men who have sex with men in coastal Kenya

Background: Men who have sex with men (MSM) have a higher prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections compared to the rest of the population, often remaining undiagnosed. In Kenya, prevalence of rectal CT and NG infection and NG antimicrobial sensitivity are poorly described. Methods: MSM who reported receptive anal intercourse (RAI) were recruited from an ongoing human immunodeficiency virus acquisition and treatment study in coastal Kenya in 2016-2017. Rectal swabs were collected at two time points 6 months apart to estimate prevalence and incidence of CT/NG infection using a molecular point-of-care assay. Participants positive for CT or NG were treated according to national guidelines. NG culture and antimicrobial susceptibility testing was performed. Participant and risk behaviour characteristics were collected and association with baseline CT/NG prevalence assessed by multivariable regression analysis. Results: Prevalence of CT/NG in 104 MSM was 21.2% (CT 13.5%, NG 9.6%, dual infection 1.9%) at baseline and 25.9% in 81 MSM at follow-up (CT 14.8%, NG 14.8%, dual infection 3.7%). CT/NG incidence was estimated at 53.0 (95% CI, 34.5-81.3) per 100 person-years. Most CT/NG positive participants were asymptomatic: 95.5% at baseline and 100% at follow-up. CT/NG infection was associated with being paid for sex [adjusted odds ratio (aOR)=6.2, 95% CI (1.7-22.9)] and being in formal employment [aOR=7.5, 95% CI (1.1-49.2)]. Six NG isolates were obtained at follow-up; all were susceptible to ceftriaxone and cefixime and all were resistant to penicillin, tetracycline and ciprofloxacin. Conclusions: There is a high prevalence and incidence of asymptomatic rectal CT and NG in MSM reporting RAI in coastal Kenya. MSM who were paid for sex or had formal employment were more likely to be infected with CT/NG suggesting increased risk behaviour during transactional sex. Antimicrobial susceptibility results suggest that current antibiotic choices in Kenya are appropriate for NG treatment.

Initial Virome Characterization of the Common Cnidarian Lab Model Nematostella vectensis.

The role of viruses in forming a stable holobiont has been the subject of extensive research in recent years. However, many emerging model organisms still lack any data on the composition of the associated viral communities. Here, we re-analyzed seven publicly available transcriptome datasets of the starlet sea anemone Nematostella vectensis, the most commonly used anthozoan lab model, and searched for viral sequences. We applied a straightforward, yet powerful approach of de novo assembly followed by homology-based virus identification and a multi-step, thorough taxonomic validation. The comparison of different lab populations of N. vectensis revealed the existence of the core virome composed of 21 viral sequences, present in all adult datasets. Unexpectedly, we observed an almost complete lack of viruses in the samples from the early developmental stages, which together with the identification of the viruses shared with the major source of the food in the lab, the brine shrimp Artemia salina, shed new light on the course of viral species acquisition in N. vectensis. Our study provides an initial, yet comprehensive insight into N. vectensis virome and sets the first foundation for the functional studies of viruses and antiviral systems in this lab model cnidarian.

Different Plant Viruses Induce Changes in Feeding Behavior of Specialist and Generalist Aphids on Common Bean That Are Likely to Enhance Virus Transmission.

Bean common mosaic virus (BCMV), bean common mosaic necrosis virus (BCMNV), and cucumber mosaic virus (CMV) cause serious epidemics in common bean (Phaseolus vulgaris), a vital food security crop in many low-to-medium income countries, particularly in Sub-Saharan Africa. Aphids transmit these viruses “non-persistently,” i.e., virions attach loosely to the insects' stylets. Viruses may manipulate aphid-host interactions to enhance transmission. We used direct observation and electrical penetration graph measurements to see if the three viruses induced similar or distinct changes in feeding behaviors of two aphid species, Aphis fabae and Myzus persicae. Both aphids vector BCMV, BCMNV, and CMV but A. fabae is a legume specialist (the dominant species in bean fields) while M. persicae is a generalist that feeds on and transmits viruses to diverse plant hosts. Aphids of both species commenced probing epidermal cells (behavior optimal for virus acquisition and inoculation) sooner on virus-infected plants than on mock-inoculated plants. Infection with CMV was especially disruptive of phloem feeding by the bean specialist aphid A. fabae. A. fabae also experienced mechanical stylet difficulty when feeding on virus-infected plants, and this was also exacerbated for M. persicae. Overall, feeding on virus-infected host plants by specialist and generalist aphids was affected in different ways but all three viruses induced similar effects on each aphid type. Specifically, non-specialist (M. persicae) aphids encountered increased stylet difficulties on plants infected with BCMV, BCMNV, or CMV, whereas specialist aphids (A. fabae) showed decreased phloem ingestion on infected plants. Probing and stylet pathway activity (which facilitate virus transmission) were not decreased by any of the viruses for either of the aphid species, except in the case of A. fabae on CMV-infected bean, where these activities were increased. Overall, these virus-induced changes in host-aphid interactions are likely to enhance non-persistent virus transmission, and data from this work will be useful in epidemiological modeling of non-persistent vectoring of viruses by aphids.

Impact of Mutations in Arabidopsis thaliana Metabolic Pathways on Polerovirus Accumulation, Aphid Performance, and Feeding Behavior.

During the process of virus acquisition by aphids, plants respond to both the virus and the aphids by mobilizing different metabolic pathways. It is conceivable that the plant metabolic responses to both aggressors may be conducive to virus acquisition. To address this question, we analyze the accumulation of the phloem-limited polerovirus Turnip yellows virus (TuYV), which is strictly transmitted by aphids, and aphid’s life traits in six Arabidopsis thaliana mutants (xth33, ss3-2, nata1, myc234, quad, atr1D, and pad4-1). We observed that mutations affecting the carbohydrate metabolism, the synthesis of a non-protein amino acid and the glucosinolate pathway had an effect on TuYV accumulation. However, the virus titer did not correlate with the virus transmission efficiency. Some mutations in A. thaliana affect the aphid feeding behavior but often only in infected plants. The duration of the phloem sap ingestion phase, together with the time preceding the first sap ingestion, affect the virus transmission rate more than the virus titer did. Our results also show that the aphids reared on infected mutant plants had a reduced biomass regardless of the mutation and the duration of the sap ingestion phase.

Mutations in the coat protein of a begomovirus result in altered transmission by different species of whitefly vectors.

For many crop pathogens including viruses, high genetic variation provides them with potential to adapt to and prevail in a changing environment. Understanding genetic variation in viruses and their significance is a key to elaborate virus epidemiology and evolution. While genetic variation of plant viruses has been documented to impact virus–host interactions, how it affects virus–insect vector interactions remains elusive. Here, we report the impact of mutations in the coat protein of squash leaf curl China virus (SLCCNV), a begomovirus, on the interaction between the virus and its whitefly vectors. We characterized mutations in the coat protein of SLCCNV and found that some residues exhibited higher mutation frequency than the others. We assayed the impact of mutation on infectivity using agroinoculation and found these mutations marginally affect virus infectivity. We further analyze their functions using virus acquisition and transmission trials and found some of mutations resulted in altered transmission of SLCCNV by different species of the whitefly Bemisia tabaci complex. We then identified the key amino acid residue(s) involved by constructing several mutant viruses and found that a single-residue mutation in the coat protein of SLCCNV was sufficient to significantly alter the whitefly transmission characteristics of SLCCNV. We examined the competition between different genotypes of SLCCNV in plant infection and whitefly transmission. We found that mutations in the coat protein did not alter the fitness of SLCCNV in plants, but they rendered the virus more competitive in transmission by certain species of whiteflies. Our findings indicate that mutations in the coat protein may play a key role in both the adaptation of begomoviruses to the changing vector populations and the evolution of begomoviruses.

Development of anti-leukemia measures in livestock farms of Kalmykia on the basis of complex diagnosis of the disease

The efficiency of diagnostic methods to control cattle leukemia during health measures in the farms of the Republic of Kalmykia was studied and a plan of anti-leukemia measures was developed. As a result, at a negative growth rate (-90.2%) the ill-being index defining the breadth of incidence in the territory of the republic was reduced by 10.2 times over 2003-2018. At the same time, while over 9 years from 2003 to 2008 the average ill-being index was within 0.42, from 2009 to 2018 it decreased from 0.33 to 0.03. The average tension coefficient, which takes into account the rate of acquisition of Bovine Leukemia Virus in the territory of the Republic by the end of the period (2018), remains zero.

Identifying Missed Opportunities for Human Immunodeficiency Virus Pre-exposure Prophylaxis During Preventive Care and Reproductive Visits in Adolescents in the Deep South.

Pre-exposure prophylaxis (PrEP) for individuals at significant risk for Human Immunodeficiency Virus acquisition is approved for individuals weighing at least 35 kg by the Food and Drug Administration. This cross-sectional study analyzed indications for PrEP in a clinical setting. There were 429 charts reviewed from adolescents between 15 and 21 years old seen for preventive care visits at an adolescent primary care center in the Deep South during a 1-year timeframe. Univariate and multivariable regression analyses were completed to identify factors associated with indications for PrEP. Forty-four percent of 429 adolescents (between 15 and 21 years) had a PrEP indication; 77% were women and 95% heterosexual. Significant factors associated with an indication for PrEP included living with a nonparent or nonrelative and polysubstance use. No adolescents with an indication for PrEP were prescribed PrEP. A sensitivity analysis comparing indications for PrEP between the 2014 and 2017 The Centers for Disease Control and Prevention Guidelines revealed no significant differences in percent with an indication (44.5% vs. 42.8%) or factors associated with indications. Pre-exposure prophylaxis as a biomedical tool for adolescents and young adults (AYAs) may remain underutilized. A key factor in improving utilization involves providers being able to recognize AYAs who may have an indication for PrEP with a specific focus on those AYAs who do not live in households with parents or a surrogate family member and those who are polysubstance users.

Infectious disease symptoms and microbial carriage among French medical students travelling abroad: A prospective study.

BackgroundIn France, no previous studies have focused specifically on health problems among medical students during internships abroad including the clinical symptoms suggestive of infectious diseases and the acquisition of pathogen carriage.MethodsClinical follow up and qPCR based respiratory, gastrointestinal and vaginal pathogen carriage before and after travel were prospectively assessed in a cohort of medical students departing from Marseille, France.Results134 students were included. 73.9%, 38.8% and 5.0% of students reported gastrointestinal, respiratory and vaginal symptoms, respectively. The acquisition rate of Enteroaggregative Escherichia coli (EAEC) and Enteropathogenic E. coli (EPEC) was 53% and 41%, respectively. The acquisition of respiratory viruses was low but associated with persisting symptoms, while bacterial acquisition ranged from 3.3% for Streptococcus pyogenes to 15.0% for Haemophilus influenzae. Gardnerella vaginalis and Atopobium vaginae acquisition rates were 7.7% and 14.3% respectively. Five students (5.1%) had molecular quantification criteria for bacterial vaginosis on return.ConclusionThis preliminary study demonstrates that besides the known risk of gastrointestinal and respiratory infections and associated changes in intestinal and respiratory microbiota, medical students abroad may also experience changes in vaginal microbiota leading, in some cases, to clinical symptoms or the acquisition of bacterial vaginosis, which may be asymptomatic.

Rectal gonorrhoea and chlamydia among men who have sex with men in coastal Kenya

Background: Men who have sex with men (MSM) have a higher prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections compared to the rest of the population, often remaining undiagnosed. In Kenya, prevalence of rectal CT and NG infection and NG antimicrobial sensitivity are poorly described. Methods: MSM who reported receptive anal intercourse (RAI) were recruited from an ongoing human immunodeficiency virus acquisition and treatment study in coastal Kenya in 2016-2017. Rectal swabs were collected at two time points 6 months apart to estimate prevalence and incidence of CT/NG infection using a molecular point-of-care assay. Participants positive for CT or NG were treated according to national guidelines. NG culture and antimicrobial susceptibility testing was performed. Participant and risk behaviour characteristics were collected and association with baseline CT/NG prevalence assessed by multivariable regression analysis. Results: Prevalence of CT/NG in 104 MSM was 21.2% (CT 13.5%, NG 9.6%, dual infection 1.9%) at baseline and 25.9% in 81 MSM at follow-up (CT 14.8%, NG 14.8%, dual infection 3.7%). CT/NG incidence was estimated at 53.0 (95% CI, 34.5-81.3) per 100 person-years. Most CT/NG positive participants were asymptomatic: 95.5% at baseline and 100% at follow-up. CT/NG infection was associated with being paid for sex [adjusted odds ratio (aOR)=6.2, 95% CI (1.7-22.9)] and being in formal employment [aOR=7.5, 95% CI (1.1-49.2)]. Six NG isolates were obtained at follow-up; all were susceptible to ceftriaxone and cefixime and all were resistant to penicillin, tetracycline and ciprofloxacin. Conclusions: There is a high prevalence and incidence of asymptomatic rectal CT and NG in MSM reporting RAI in coastal Kenya. MSM who were paid for sex or had formal employment were more likely to be infected with CT/NG suggesting increased risk behaviour during transactional sex. Antimicrobial susceptibility results suggest that current antibiotic choices in Kenya are appropriate for NG treatment.

Rectal gonorrhoea and chlamydia among men who have sex with men in coastal Kenya

Background: Men who have sex with men (MSM) have a higher prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections compared to the rest of the population, often remaining undiagnosed. In Kenya, prevalence of rectal CT and NG infection and NG antimicrobial sensitivity are poorly described. Methods: MSM who reported receptive anal intercourse (RAI) were recruited from an ongoing human immunodeficiency virus acquisition and treatment study in coastal Kenya in 2016-2017. Rectal swabs were collected at two time points 6 months apart to estimate prevalence and incidence of CT/NG infection using a molecular point-of-care assay. Participants positive for CT or NG were treated according to national guidelines. NG culture and antimicrobial susceptibility testing was performed. Participant and risk behaviour characteristics were collected and association with baseline CT/NG prevalence assessed by multivariable regression analysis. Results: Prevalence of CT/NG in 104 MSM was 21.2% (CT 13.5%, NG 9.6%, dual infection 1.9%) at baseline and 25.9% in 81 MSM at follow-up (CT 14.8%, NG 14.8%, dual infection 3.7%). CT/NG incidence was estimated at 53.0 (95% CI, 34.5-81.3) per 100 person-years. Most CT/NG positive participants were asymptomatic: 95.5% at baseline and 100% at follow-up. CT/NG infection was associated with being paid for sex [adjusted odds ratio (aOR)=6.2, 95% CI (1.7-22.9)] and being in formal employment [aOR=7.5, 95% CI (1.1-49.2)]. Six NG isolates were obtained at follow-up; all were susceptible to ceftriaxone and cefixime and all were resistant to penicillin, tetracycline and ciprofloxacin. Conclusions: There is a high prevalence and incidence of asymptomatic rectal CT and NG in MSM reporting RAI in coastal Kenya. MSM who were paid for sex or had formal employment were more likely to be infected with CT/NG suggesting increased risk behaviour during transactional sex. Antimicrobial susceptibility results suggest that current antibiotic choices in Kenya are appropriate for NG treatment.

ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type.

The ALVAC-HIV clade B/AE and equivalent SIV-based/gp120 + Alum vaccines successfully decreased the risk of virus acquisition in humans and macaques. Here, we tested the efficacy of HIV clade B/C ALVAC/gp120 vaccine candidates + MF59 or different doses of Aluminum hydroxide (Alum) against SHIV-Cs of varying neutralization sensitivity in macaques. Low doses of Alum induced higher mucosal V2-specific IgA that increased the risk of Tier 2 SHIV-C acquisition. High Alum dosage, in contrast, elicited serum IgG to V2 that correlated with a decreased risk of Tier 1 SHIV-C acquisition. MF59 induced negligible mucosal antibodies to V2 and an inflammatory profile with blood C-reactive Protein (CRP) levels correlating with neutralizing antibody titers. MF59 decreased the risk of Tier 1 SHIV-C acquisition. The relationship between vaccine efficacy and the neutralization profile of the challenge virus appear to be linked to the different immunological spaces created by MF59 and Alum via CXCL10 and IL-1β, respectively.

Maize Iranian mosaic virus (family Rhabdoviridae) improves biological traits of its vector Laodelphax striatellus.

Plant viruses can alter the behavior or performance of their arthropod vectors, either indirectly (through effects of virus infection on the host plant) or directly (from virus acquisition by the vector). Given the diversity of plant viruses and their arthropod vectors, the effects for any specific system are not possible to predict. Here, we present experimental evidence that acquisition of maize Iranian mosaic virus (MIMV, genus Nucleorhabdovirus, family Rhabdoviridae) modifies the biological traits of its insect vector, the small brown planthopper (SBPH) Laodelphax striatellus. MIMV is an economically important virus of maize and several other grass species. It is transmitted by SBPHs in a persistent-propagative manner. We evaluated the effects of MIMV acquisition by SBPH on its life history when reared on healthy barley plants (Hordeum vulgare). We conclude that 1)MIMV acquisition by SBPHs increasesfemale fecundity, duration of the nymph stage, adult longevity, and survival of SBPHs, (2) the mortality rate and female-to-male sex ratio are reduced in MIMV-infected planthoppers, and (3) MIMV infection increases the concentration of some biochemical components of the infected plants, including carbohydrates, some amino acids, and total protein, which might influence the life traits of its insect vector. The results indicate the potential of MIMV to improve the ecological fitness of its vector, SBPH, through direct or indirect effects, with the potential to increase the spread of the virus.

Investigating the Movement Components of Host Preference in a Highly Mobile Insect Herbivore, Nephotettix cincticeps (Hemiptera: Cicadellidae).

Effective insect management strategies require a firm understanding of the factors determining host preference, particularly in highly mobile insect herbivores. Host preference studies commonly employ average or first position as a proxy for preference. Yet few studies have explored host preference in relation to transitory attraction and leaving rates, yet these are both components of host plant selection. We investigated the transitory dynamics of preference by the green rice leafhopper, Nephotettix cincticeps (Uhler) (Hemiptera: Cicadellidae) by conducting experiments on groups of females, males, or mixed-sex leafhoppers, and recording their position over time between low-N and normal-N rice plants. Utilizing a log-linear model and variants of a biostatistical model we used these positional data to extract attraction, leaving and tenure rates to better understand the process of host-plant selection. We found a general preference for normal-N over low-N plants at equilibrium. However, between sexes there was variation in the relative significance of attraction or leaving rates on that preference. Female leafhoppers were more attracted to host plants with higher nitrogen content. Male leafhoppers were less discriminate in their initial attraction to hosts but left low-N hosts at a faster rate. Whereas estimated tenure times on both normal- and low-N plants exceeded transmission times for the leafhopper-transmitted rice dwarf virus, longer tenure on normal-N plants likely increases the likelihood of virus acquisition from these plants. Our findings support previous recommendations that growers can mitigate the risks of leafhopper damage and pathogen transmission by optimizing their application of nitrogenous fertilizers.

Predictive biomarkers for cognitive decline during progressive HIV infection.

Predictive biomarkers for cognitive decline during progressive HIV infection.

Machine Learning to Identify Persons at High-Risk of Human Immunodeficiency Virus Acquisition in Rural Kenya and Uganda.

In generalized epidemic settings, strategies are needed to prioritize individuals at higher risk of human immunodeficiency virus (HIV) acquisition for prevention services. We used population-level HIV testing data from rural Kenya and Uganda to construct HIV risk scores and assessed their ability to identify seroconversions. During 2013-2017, >75% of residents in 16 communities in the SEARCH study were tested annually for HIV. In this population, we evaluated 3 strategies for using demographic factors to predict the 1-year risk of HIV seroconversion: membership in ≥1 known "risk group" (eg, having a spouse living with HIV), a "model-based" risk score constructed with logistic regression, and a "machine learning" risk score constructed with the Super Learner algorithm. We hypothesized machine learning would identify high-risk individuals more efficiently (fewer persons targeted for a fixed sensitivity) and with higher sensitivity (for a fixed number targeted) than either other approach. A total of 75 558 persons contributed 166 723 person-years of follow-up; 519 seroconverted. Machine learning improved efficiency. To achieve a fixed sensitivity of 50%, the risk-group strategy targeted 42% of the population, the model-based strategy targeted 27%, and machine learning targeted 18%. Machine learning also improved sensitivity. With an upper limit of 45% targeted, the risk-group strategy correctly classified 58% of seroconversions, the model-based strategy 68%, and machine learning 78%. Machine learning improved classification of individuals at risk of HIV acquisition compared with a model-based approach or reliance on known risk groups and could inform targeting of prevention strategies in generalized epidemic settings. NCT01864603.

PD-1 Blockade and TLR7 Activation Lack Therapeutic Benefit in Chronic Simian Immunodeficiency Virus-Infected Macaques on Antiretroviral Therapy.

Antiretroviral therapy (ART) limits human immunodeficiency virus 1 (HIV-1) replication but does not eliminate the long-lived reservoir established shortly after viral acquisition. A successful HIV cure intervention necessitates either elimination or generation of long-term immune control of the persistent viral reservoir. Immune modulating strategies in conjunction with ART hold promise for achieving cure by inducing viral antigen expression and augmenting infected cell killing. Programmed death-1 (PD-1) blockade is a potential means to both activate and eliminate the latent reservoir by restoring exhausted T cell function. We assessed the therapeutic efficacy of PD-1 blockade, Toll-like receptor 7 (TLR7) activation with the agonist vesatolimod, or a combination of the two agents in chronically simian immunodeficiency virus (SIV)-infected macaques suppressed with ART for more than 2 years. Despite achieving extended anti-PD-1 antibody plasma exposure and TLR7-dependent immune activation after multiple administrations, neither individual treatment nor the combination resulted in changes to viral rebound kinetics following ART interruption or reduction in the SIV reservoir size. Our data in the context of other reports demonstrating improved viral control upon PD-1 blockade suggest that its therapeutic utility may be restricted to specific experimental conditions or treatment times during viral pathogenesis.

A vaccine containing highly purified virus particles in adjuvant provides high level protection against genital infection and disease in guinea pigs challenged intravaginally with homologous and heterologous strains of herpes simplex virus type 2

Infection with Herpes Simplex Viruses (HSVs) represents a significant health burden worldwide with HSV-1 and HSV-2 causing genital disease and HSV-2 contributing to human immunodeficiency virus acquisition. Despite great need, there is currently no licensed vaccine against HSV. In this report, we evaluated the protective efficacy of a vaccine containing highly purified, inactivated HSV-2 particles (with and without additional recombinant glycoprotein D) formulated with a monophosphoryl lipid A/Alhydrogel adjuvant in a guinea pig HSV genital model. The key results from 3 independent studies were: (1) vaccination consistently provided significant 3–3.5 Log10 reductions in vaginal HSV-2 titers on day 2 postchallenge; (2) following homologous or heterologous challenge with two U.S. isolates, all vaccine groups showed complete protection against lesion formation, significant 3 Log10 reductions in day 2 virus shedding, enhanced virus clearance, significant reductions in HSV-2 DNA within ganglia, and no detectable shedding (<2 PFU) or latent viral DNA in some immunized animals; (3) following challenge with a third heterologous strain, vaccination provided complete protection against primary and recurrent lesions, significant reductions in primary virus shedding, a 50% reduction in recurrent shedding days, and undetectable latent virus in the ganglia and spinal cords of most animals; and (4) adding glycoprotein D provided no enhanced protection relative to that elicited by the inactivated HSV-2 particles alone. Together, these data provide strong support for further development of this exceedingly protective and highly feasible vaccine candidate for human trials.

Silencing of Odorant-Binding Protein Gene OBP3 Using RNA Interference Reduced Virus Transmission of Tomato Chlorosis Virus.

Tomato chlorosis virus (ToCV) is widespread, seriously impacting tomato production throughout the world. ToCV is semi-persistently transmitted by Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). Currently, insect olfaction is being studied to develop novel pest control technologies to effectively control B. tabaci and whitefly-borne virus diseases. Despite current research efforts, no report has been published on the role of odorant-binding proteins (OBPs) in insect preference under the influence of plant virus. Our previous research showed that viruliferous B. tabaci preferred healthy plants at 48 h after virus acquisition. In this study, we determined the effect of OBPs on the host preference interactions of ToCV and whiteflies. Our results show that with the increase in acquisition time, the OBP gene expressions changed differently, and the OBP3 gene expression showed a trend of first rising and then falling, and reached the maximum at 48 h. These results indicate that OBP3 may participate in the host preference of viruliferous whiteflies to healthy plants. When the expression of the OBP3 gene was knocked down by an RNA interference (RNAi) technique, viruliferous Mediterranean (MED) showed no preference and the ToCV transmission rate was reduced by 83.3%. We conclude that OBP3 is involved in the detection of plant volatiles by viruliferous MED. Our results provide a theoretical basis and technical support for clarifying the transmission mechanism of ToCV by B. tabaci and could provide new avenues for controlling this plant virus and its vectors.