scholarly journals Number of HIV-1 founder variants is determined by the recency of the source partner infection

Science ◽  
2020 ◽  
Vol 369 (6499) ◽  
pp. 103-108 ◽  
Author(s):  
Ch. Julián Villabona-Arenas ◽  
Matthew Hall ◽  
Katrina A. Lythgoe ◽  
Stephen G. Gaffney ◽  
Roland R. Regoes ◽  
...  
Keyword(s):  
Early Stage ◽  
Control Strategies ◽  
Sexual Transmission ◽  
Low Frequency ◽  
Epidemiological Data ◽  
High Genetic Diversity ◽  
Partner Characteristics ◽  
Infection Stage ◽  
Hiv 1 ◽  
Founder Strain

During sexual transmission, the high genetic diversity of HIV-1 within an individual is frequently reduced to one founder variant that initiates infection. Understanding the drivers of this bottleneck is crucial to developing effective infection control strategies. Little is known about the importance of the source partner during this bottleneck. To test the hypothesis that the source partner affects the number of HIV founder variants, we developed a phylodynamic model calibrated using genetic and epidemiological data on all existing transmission pairs for whom the direction of transmission and the infection stage of the source partner are known. Our results suggest that acquiring infection from someone in the acute (early) stage of infection increases the risk of multiple–founder variant transmission compared with acquiring infection from someone in the chronic (later) stage of infection. This study provides the first direct test of source partner characteristics to explain the low frequency of multiple–founder strain infections.

scholarly journals HIV-1 founder variant multiplicity is determined by the infection stage of the source partner

2019 ◽  
Author(s):  
Ch. Julián Villabona-Arenas ◽  
Matthew Hall ◽  
Katrina A. Lythgoe ◽  
Stephen G. Gaffney ◽  
Roland R. Regoes ◽  
...  
Keyword(s):  
Early Stage ◽  
Control Strategies ◽  
Sexual Transmission ◽  
Low Frequency ◽  
Clinical Intervention ◽  
Epidemiological Data ◽  
Genetic Characteristics ◽  
Partner Characteristics ◽  
Infection Stage ◽  
Hiv 1

AbstractDuring sexual transmission, the large genetic diversity of HIV-1 within an individual is frequently reduced to one founder variant that initiates infection 1. Understanding the drivers of this bottleneck is crucial to develop effective infection control strategies 2. Genetic characteristics of the potential founder viruses and events in the recipient partner are both known to contribute to this bottleneck, but little is understood about the importance of the source partner 3. To test the hypothesis that the source partner affects the multiplicity of HIV founder variants, we developed a phylodynamic model calibrated using genetic and epidemiological data on all existing transmission pairs for whom the direction of transmission and the infection stage of the source partner are known. Our results demonstrate the importance of infection stage of the source partner, and not exposure route, in determining founder variant multiplicity. Specifically, acquiring infection from someone in the acute (early) stage of infection increases the risk of multiple variant transmission when compared with someone in the chronic (later) stage of infection. This study provides the first direct test of source partner characteristics to explain the low frequency of multiple founder strain infections and can inform clinical intervention study design and interpretation.

scholarly journals HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 475 ◽  
Author(s):  
Madita Schlösser ◽  
Vladimir V. Kartashev ◽  
Visa H. Mikkola ◽  
Andrey Shemshura ◽  
Sergey Saukhat ◽  
...  
Keyword(s):  
Low Frequency ◽  
Federal District ◽  
Epidemiological Data ◽  
Epidemiological Studies ◽  
Heterosexual Contact ◽  
Hiv Epidemiology ◽  
Subtype B ◽  
Accurate Knowledge ◽  
Systematic Identification ◽  
Hiv 1

Russia has one of the largest and fastest growing HIV epidemics. However, epidemiological data are scarce. Sub-subtype A6 is most prevalent in Russia but its identification is challenging. We analysed protease/reverse transcriptase-, integrase-sequences, and epidemiological data from 303 patients to develop a methodology for the systematisation of A6 identification and to describe the HIV epidemiology in the Russian Southern Federal District. Drug consumption (32.0%) and heterosexual contact (27.1%) were the major reported transmission risks. This study successfully established the settings for systematic identification of A6 samples. Low frequency of subtype B (3.3%) and large prevalence of sub-subtype A6 (69.6%) and subtype G (23.4%) were detected. Transmitted PI- (8.8%) and NRTI-resistance (6.4%) were detected in therapy-naive patients. In therapy-experienced patients, 17.3% of the isolates showed resistance to PIs, 50.0% to NRTI, 39.2% to NNRTIs, and 9.5% to INSTIs. Multiresistance was identified in 52 isolates, 40 corresponding to two-class resistance and seven to three-class resistance. Two resistance-associated-mutations significantly associated to sub-subtype A6 samples: A62VRT and G190SRT. This study establishes the conditions for a systematic annotation of sub-subtype A6 to normalise epidemiological studies. Accurate knowledge on South Russian epidemiology will allow for the development of efficient regional frameworks for HIV-1 infection management.

scholarly journals Variability in HIV-1 Integrase Gene and 3′-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy

2020 ◽  
Vol 21 (5) ◽  
pp. 1553 ◽  
Author(s):  
Arpan Acharya ◽  
Claude T. Tagny ◽  
Dora Mbanya ◽  
Julius Y. Fonsah ◽  
Emilienne Nchindap ◽  
...  
Keyword(s):  
Low Frequency ◽  
Clinical Samples ◽  
Strand Transfer ◽  
African Countries ◽  
High Genetic Diversity ◽  
Integrase Gene ◽  
Infected People ◽  
Polypurine Tract ◽  
Clade B ◽  
Hiv 1

Integrase strand-transfer inhibitors (INSTIs) are now included in preferred first-line antiretroviral therapy (ART) for HIV-infected adults. Studies of Western clade-B HIV-1 show increased resistance to INSTIs following mutations in integrase and nef 3′polypurine tract (3′-PPT). With anticipated shifts in Africa (where 25.6-million HIV-infected people resides) to INSTIs-based ART, it is critical to monitor patients in African countries for resistance-associated mutations (RAMs) affecting INSTIs efficacy. We analyzed HIV-1 integrase and 3′-PPT sequences in 345 clinical samples from INSTIs-naïve HIV-infected Cameroonians for polymorphisms and RAMs that affect INSTIs. Phylogeny showed high genetic diversity, with the predominance of HIV-1 CRF02_AG. Major INSTIs RAMs T66A and N155K were found in two (0.6%) samples. Integrase polymorphic and accessory RAMs found included T97A, E157Q, A128T, M50I, S119R, L74M, L74I, S230N, and E138D (0.3′23.5% of samples). Ten (3.2%) samples had both I72V+L74M, L74M+T97A, or I72V+T97A mutations; thirty-one (9.8%) had 3′-PPT mutations. The low frequency of major INSTIs RAMs shows that INSTIs-based ART can be successfully used in Cameroon. Several samples had ≥1 INSTIs accessory RAMs known to reduce INSTIs efficacy; thus, INSTIs-based ART would require genetic surveillance. The 3′-PPT mutations could also affect INSTIs. For patients failing INSTIs-based ART with no INSTIs RAMs, monitoring 3′-PPT sequences could reveal treatment failure etiology.

scholarly journals Tracing the origin and dynamics of the HIV-1 epidemic in Serbia

2014 ◽  
Vol 66 (2) ◽  
pp. 507-515 ◽  
Author(s):  
Marina Siljic ◽  
Dubravka Salemovic ◽  
Dj. Jevtovic ◽  
Ivana Pesic-Pavlovic ◽  
Sonja Zerjav ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Sexual Transmission ◽  
Intravenous Drug User ◽  
Subtype C ◽  
Subtype B ◽  
Sex With Men ◽  
Hiv 1 ◽  
Genetic Form ◽  
Subtype Distribution ◽  
Founder Strain

Since the first report of HIV infection in Serbia in 1985, the HIV-1 epidemic was very dynamic, changing the pattern in subtype distribution and prevailing transmission routes. To better understand the origin and epidemiological dynamics of HIV-1, we analyzed 266 (pol) sequences from Serbian patients diagnosed over a period of 14 years. Subtype distribution in Serbia is still marked by a prevailing subtype B genetic form. The transmission pattern, however, has changed from being intravenous drug user (IVDU) - driven to predominantly sexual transmission. The estimated time of initial founder strain introduction of sequences from Serbian IVDUs and MSM (men who have sex with men) is similar and dates back to the early 1980s, while introduction of subtype C occurred much more recently.

Novel Coronavirus SARS-CoV-2 (COVID-19) and Pregnancy: A hypothetical view

2020 ◽  
Vol 20 ◽  
Author(s):  
Ahmed RG
Keyword(s):  
Immune System ◽  
Cellular Therapy ◽  
Early Stage ◽  
Control Strategies ◽  
Vital Role ◽  
Healthy Life ◽  
Global Pandemic ◽  
Maternal Immune System ◽  
Perinatal Management ◽  
Novel Coronavirus

Background: The complications of the SARS-CoV-2 infection and its COVID-19 disease on mothers and their offspring are less known. Objective: The aim of this review was to determine the transmission, severity, complications of SARS-CoV-2 infection during the pregnancy. This review showed the influence of COVID-19 disease on the neonatal neurogenesis. Owing to no specific vaccines or medicines that were reported for the treatment of COVID-19 disease, this review suggested some control strategies like treatments (medicinal plants, antiviral therapy, cellular therapy, and immunotherapy), nutrition uptake, prevention, and recommendations. Discussion: This overview showed in severely states that SARS-CoV-2 infection during the early stage of pregnancy might increase the risk of stress, panic, and anxiety. This disorder can disturb the maternal immune system, and thus causing a neurodevelopmental disturbance. This hypothesis may be depending on the severity and intensity of the SARS-CoV-2 infection during pregnancy. However, vertical transmission of SARS-CoV-2 from dams to their fetuses is absent until now. Conclusion: During this global pandemic disease, maintaining safety during pregnancy, vaginal delivery, and breastfeeding may play a vital role in a healthy life for the offspring. Thus, international and national corporations should be continuing for perinatal management, particularly during the next pandemic or disaster time.

scholarly journals Symptom-based early-stage differentiation between SARS-CoV-2 versus other respiratory tract infections—Upper Silesia pilot study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Justyna Mika ◽  
Joanna Tobiasz ◽  
Joanna Zyla ◽  
Anna Papiez ◽  
Małgorzata Bach ◽  
...  
Keyword(s):  
Pilot Study ◽  
Body Temperature ◽  
Respiratory Tract ◽  
Older Patients ◽  
Respiratory Tract Infections ◽  
Early Stage ◽  
Patient Groups ◽  
Project Data ◽  
Tract Infections ◽  
Infection Stage

AbstractIn the DECODE project, data were collected from 3,114 surveys filled by symptomatic patients RT-qPCR tested for SARS-CoV-2 in a single university centre in March-September 2020. The population demonstrated balanced sex and age with 759 SARS-CoV-2( +) patients. The most discriminative symptoms in SARS-CoV-2( +) patients at early infection stage were loss of taste/smell (OR = 3.33, p < 0.0001), body temperature above 38℃ (OR = 1.67, p < 0.0001), muscle aches (OR = 1.30, p = 0.0242), headache (OR = 1.27, p = 0.0405), cough (OR = 1.26, p = 0.0477). Dyspnea was more often reported among SARS-CoV-2(-) (OR = 0.55, p < 0.0001). Cough and dyspnea were 3.5 times more frequent among SARS-CoV-2(-) (OR = 0.28, p < 0.0001). Co-occurrence of cough, muscle aches, headache, loss of taste/smell (OR = 4.72, p = 0.0015) appeared significant, although co-occurrence of two symptoms only, cough and loss of smell or taste, means OR = 2.49 (p < 0.0001). Temperature > 38℃ with cough was most frequent in men (20%), while loss of taste/smell with cough in women (17%). For younger people, taste/smell impairment is sufficient to characterise infection, whereas in older patients co-occurrence of fever and cough is necessary. The presented study objectifies the single symptoms and interactions significance in COVID-19 diagnoses and demonstrates diverse symptomatology in patient groups.

scholarly journals Analysis of Low-Frequency Mutations Associated with Drug Resistance to Raltegravir before Antiretroviral Treatment

2010 ◽  
Vol 55 (3) ◽  
pp. 1114-1119 ◽  
Author(s):  
Jia Liu ◽  
Michael D. Miller ◽  
Robert M. Danovich ◽  
Nathan Vandergrift ◽  
Fangping Cai ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Failure ◽  
Low Frequency ◽  
Hiv Treatment ◽  
Viral Population ◽  
Virologic Suppression ◽  
Resistance Mutations ◽  
The Difference ◽  
Allele Specific Sequencing ◽  
Hiv 1

ABSTRACTRaltegravir is highly efficacious in the treatment of HIV-1 infection. The prevalence and impact on virologic outcome of low-frequency resistant mutations among HIV-1-infected patients not previously treated with raltegravir have not been fully established. Samples from HIV treatment-experienced patients entering a clinical trial of raltegravir treatment were analyzed using a parallel allele-specific sequencing (PASS) assay that assessed six primary and six secondary integrase mutations. Patients who achieved and sustained virologic suppression (success patients,n= 36) and those who experienced virologic rebound (failure patients,n= 35) were compared. Patients who experienced treatment failure had twice as many raltegravir-associated resistance mutations prior to initiating treatment as those who achieved sustained virologic success, but the difference was not statistically significant. The frequency of nearly all detected resistance mutations was less than 1% of viral population, and the frequencies of mutations between the success and failure groups were similar. Expansion of pre-existing mutations (one primary and five secondary) was observed in 16 treatment failure patients in whom minority resistant mutations were detected at baseline, suggesting that they might play a role in the development of drug resistance. Two or more mutations were found in 13 patients (18.3%), but multiple mutations were not present in any single viral genome by linkage analysis. Our study demonstrates that low-frequency primary RAL-resistant mutations were uncommon, while minority secondary RAL-resistant mutations were more frequently detected in patients naïve to raltegravir. Additional studies in larger populations are warranted to fully understand the clinical implications of these mutations.

The Investigation of the Optimization Scheme of the Low-cycle Fatigue Cropping Based on the Acoustic Emission Technique

2021 ◽  
Author(s):  
Yujian Ren ◽  
Jingxiang Li ◽  
Yuanzhe Dong ◽  
Dong Jin ◽  
Shengdun Zhao
Keyword(s):  
Acoustic Emission ◽  
High Frequency ◽  
Control Method ◽  
Low Cycle Fatigue ◽  
Control Strategies ◽  
Low Frequency ◽  
Loading Frequency ◽  
Cycle Fatigue ◽  
Al 6061 ◽  
Whole Process

Abstract High efficiency and good section quality are two main objectives of metal bar cropping. A suitable control method can help to achieve both goals. An investigation of the control method of low-cycle fatigue cropping (LCFC) based on the acoustic emission (AE) technique has been proposed in this study. Ring-down counts and kurtosis are used to monitor the whole process of LCFC. The results showed that kurtosis is more suitable for monitoring the LCFC process and as a critical parameter to optimize the control method than ring-down counts in the noisy factory environment.Moreover, three types of materials are studied in this experiment; by combine with the AE results, macroscopic images and microscopic images of sections, characteristics of various LCFC stages are obtained. The results also indicated reduce the area of the transient fracture zone is the key to improve the section quality. Reducing the load frequency before the unstable crack propagation stage will beneficial to realize the goals. Based on the evaluation of kurtosis, an optimized control method is presented, and two control parameters: transient time T and the critical value of the slope of kurtosis C are determined. For 16Mn, 1045 and Al 6061, the T is 5s, 10s, and 1s, respectively. For 16Mn, 1045, and Al 6061, the C is 100, 300, and 0, respectively. Two parameters, h and S, are used to evaluate the section quality and four control strategies are compared. The results indicate the optimal control methods can improve the section quality effectively. The influence trend of reducing loading frequency is investigated by further comparison. It can be seen as the frequency decreases, the efficiency of the section quality improving decreases. In order to realize the optimal results, different control strategies are adopted for different materials. Strategy 1 (high frequency is 20Hz，high frequency thought the whole process), strategy 2 (high frequency is 20Hz，low frequency is 8.33Hz), and strategy 3 (high frequency is 20Hz，low frequency is 6.67Hz) is suitable for Al 6061, 1045, and 16Mn, respectively.

Frequency-Weighted Variable-Length Controllers Using Anytime Control Strategies

2011 ◽  
Author(s):  
Gundula B. Runge ◽  
Al Ferri ◽  
Bonnie Ferri
Keyword(s):  
Time Scale ◽  
Weighting Function ◽  
Control Strategies ◽  
Low Frequency ◽  
Low Frequencies ◽  
High Frequencies ◽  
Frequency Components ◽  
Computational Resources ◽  
Weighted Variable ◽  
Selection Of

This paper considers an anytime strategy to implement controllers that react to changing computational resources. The anytime controllers developed in this paper are suitable for cases when the time scale of switching is in the order of the task execution time, that is, on the time scale found commonly with sporadically missed deadlines. This paper extends the prior work by developing frequency-weighted anytime controllers. The selection of the weighting function is driven by the expectation of the situations that would require anytime operation. For example, if the anytime operation is due to occasional and isolated missed deadlines, then the weighting on high frequencies should be larger than that for low frequencies. Low frequency components will have a smaller change over one sample time, so failing to update these components for one sample period will have less effect than with the high frequency components. An example will be included that applies the anytime control strategy to a model of a DC motor with deadzone and saturation nonlinearities.

scholarly journals ADS-J1 Inhibits Semen-Derived Amyloid Fibril Formation and Blocks Fibril-Mediated Enhancement of HIV-1 Infection

2015 ◽  
Vol 59 (9) ◽  
pp. 5123-5134 ◽  
Author(s):  
Tianrong Xun ◽  
Wenjuan Li ◽  
Jinquan Chen ◽  
Fei Yu ◽  
Wei Xu ◽  
...  
Keyword(s):  
Viral Infection ◽  
Amyloid Fibrils ◽  
Synergistic Effects ◽  
Sexual Transmission ◽  
Prostatic Acid Phosphatase ◽  
Fibril Formation ◽  
Antiretroviral Drugs ◽  
Target Cells ◽  
Additional Function ◽  
Hiv 1

ABSTRACTSemen-derived enhancer of viral infection (SEVI) is composed of amyloid fibrils that can greatly enhance HIV-1 infectivity. By its cationic property, SEVI promotes viral sexual transmission by facilitating the attachment and internalization of HIV-1 to target cells. Therefore, semen-derived amyloid fibrils are potential targets for microbicide design. ADS-J1 is an anionic HIV-1 entry inhibitor. In this study, we explored an additional function of ADS-J1: inhibition of SEVI fibril formation and blockage of SEVI-mediated enhancement of viral infection. We found that ADS-J1 bound to an amyloidogenic peptide fragment (PAP248–286, comprising amino acids 248 to 286 of the enzyme prostatic acid phosphatase), thereby inhibiting peptide assembly into amyloid fibrils. In addition, ADS-J1 binds to mature amyloid fibrils and antagonizes fibril-mediated enhancement of viral infection. Unlike cellulose sulfate, a polyanion that failed in clinical trial to prevent HIV-1 sexual transmission, ADS-J1 shows no ability to facilitate fibril formation. More importantly, the combination of ADS-J1 with several antiretroviral drugs exhibited synergistic effects against HIV-1 infection in semen, with little cytotoxicity to vaginal epithelial cells. Our results suggest that ADS-J1 or a derivative may be incorporated into a combination microbicide for prevention of the sexual transmission of HIV-1.

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