Challenges in interpreting SARS-CoV-2 serological results in African countries

A diagnosis of COVID-19 is based on a positive PCR test for SARS-CoV-2. Over the past year, PCR testing capacity has varied globally due to the availability of tests, and testing strategies have targeted mainly symptomatic individuals. Therefore, the spread of the virus is probably wider than the numbers reported by official surveillance systems that are based on PCR results. Serology tests detect antibodies against SARS-CoV-2, which start being measurable around 1–2 weeks after infection. They are used in seroprevalence studies to estimate the proportion of people in a population that has been infected, including asymptomatic infection. These studies are of particular importance in African countries, where reported testing and incidence are among the lowest in the world.Peer Reviewe

Identification of a highly conserved valine-glycine-phenylalanine amino acid triplet required for HIV-1 Nef function

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Analysis of infectious virus clones from two HIV-1 superinfection cases suggests that the primary strains have lower fitness

<p>Abstract</p> <p>Background</p> <p>Two HIV-1 positive patients, L and P, participating in the Amsterdam Cohort studies acquired an HIV-1 superinfection within half a year from their primary HIV-1 infection (Jurriaans <it>et al</it>., <it>JAIDS </it>2008, <b>47:</b>69-73). The aim of this study was to compare the replicative fitness of the primary and superinfecting HIV-1 strains of both patients. The use of isolate-specific primer sets indicated that the primary and secondary strains co-exist in plasma at all time points after the moment of superinfection.</p> <p>Results</p> <p>Biological HIV-1 clones were derived from peripheral blood CD4 + T cells at different time point, and identified as the primary or secondary virus through sequence analysis. Replication competition assays were performed with selected virus pairs in PHA/IL-2 activated peripheral blood mononuclear cells (PBMC's) and analyzed with the Heteroduplex Tracking Assay (HTA) and isolate-specific PCR amplification. In both cases, we found a replicative advantage of the secondary HIV-1 strain over the primary virus. Full-length HIV-1 genomes were sequenced to find possible explanations for the difference in replication capacity. Mutations that could negatively affect viral replication were identified in the primary infecting strains. In patient L, the primary strain has two insertions in the LTR promoter, combined with a mutation in the <it>tat </it>gene that has been associated with decreased replication capacity. The primary HIV-1 strain isolated from patient P has two mutations in the LTR that have been associated with a reduced replication rate. In a luciferase assay, only the LTR from the primary virus of patient P had lower transcriptional activity compared with the superinfecting virus.</p> <p>Conclusions</p> <p>These preliminary findings suggest the interesting scenario that superinfection occurs preferentially in patients infected with a relatively attenuated HIV-1 isolate.</p

Primate lentiviral Nef proteins deregulate T-cell development by multiple mechanisms

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The CD147 protein complex is involved in entry of Chikungunya virus and related alphaviruses in human cells

Chikungunya virus (CHIKV) is an arbovirus with a global spread and significant public health impact. It is a positive stranded RNA alphavirus belonging to the Togaviridae family. However, many questions about the replication cycle of CHIKV remain unanswered. The entry process of CHIKV is not completely understood nor are the associated virus-receptor interactions fully identified. Here, we designed an affinity purification mass spectrometry coupled approach that allowed the identification of factors that facilitate entry of CHIKV in human cells. The identified entry factors were further validated using CRISPR/Cas9. In HEK293T cells we identified the CD147 protein complex as an entry factor for CHIKV. We further showed the involvement of the CD147 protein complex in the replication cycle of related alphaviruses. Interestingly, CD147 contains similar protein domains as the previously identified alphavirus entry factor MXRA8

Chikungunya virus infection in Aruba: Diagnosis, clinical features and predictors of post-chikungunya chronic polyarthralgia

BACKGROUND: Chikungunya virus (CHIKV) emerged in Aruba for the first time in 2014. We studied the clinical presentation of acute CHIKV infection and the contribution of serologic and molecular assays to its diagnosis. In a cohort of confirmed CHIKV cases, we analysed the frequency, duration and predictors of post-chikungunya chronic polyarthralgia (pCHIK-CPA), defined as joint pains lasting longer than 6 weeks or longer than 1 year. METHODOLOGY: Patient sera obtained within 10 days of symptom onset were tested for CHIKV, using an indirect immunofluorescence test for the detection of CHIKV-specific Immunoglobulin M (IgM) and post-hoc, by reverse-transcription polymerase chain reaction (RT-PCR). CHIKV was isolated from selected samples and genotyped. For confirmed CHIKV cases, clinical data from chart review were complemented by a Telephone survey, conducted 18-24 months after diagnosis. When joint pain was reported, the duration, presence of inflammatory signs, type and number of joints affected, were recorded. Joint involvement was scored according to the 2010 'American College of Rheumatology/ European League Against Rheumatism' criteria for seronegative rheumatoid arthritis (ACR-score). Risk factors for pCHIK-CPA were identified by logistic regression. PRINCIPAL FINDINGS: Acute CHIKV infection was diagnosed in 269 of 498 sera, by detection of IgM (n = 105), by RT-PCR (n = 59), or by both methods (n = 105). Asian genotype was confirmed in 7 samples. Clinical data were complete for 171 of 248 (69.0%) patients, aged 15 years or older (median 49.4 [35.0-59.6]). The female-to-male ratio was 2.2. The main acute symptoms were arthralgia (94%), fever (85%), myalgia (85%), headache (73%) and rash (63%). In patients with arthralgia (n = 160), pCHIK-CPA longer than 6 weeks was reported by 44% and longer than 1 year by 26% of cases. Inflammatory signs, stiffness, edema and redness were frequent (71%, 39% and 21%, respectively). Joints involved were knees (66%), ankles (50%), fingers (52%), feet (46%), shoulders (36%), elbows (34%), wrists (35%), hips (31%), toes (28.1%) and spine (28.1%). Independent predictors of pCHIK-CPA longer than 1 year were female gender (OR 5.9, 95%-CI [2.1-19.6]); high ACR-score (7.4, [2.7-23.3]), and detection of CHIKV-RNA in serum beyond 7 days of symptom onset (6.4, [1.4-34.1]. CONCLUSIONS: We identified 269 CHIKV patients after the first outbreak of Asian genotype CHIKV in Aruba in 2014-2015. RT-PCR yielded 59 (28%) additional CHIKV diagnoses compared to IgM antibody detection alone. Arthralgia, fever and skin rash were the dominant acute phase symptoms. pCHIK-CPA longer than 1 year affected 26% of cases and was predicted by female gender, high ACR-score and CHIKV-RNA detection beyond 7 days of symptom onset.status: publishe

Combination index for IFN-α and IFN-λ1 against CCHF replication respectively in A549 and HuH-7 cells.

<p>*The Combination Index (CI) was calculated using the CompuSyn software (Chou, T.-C. and Martin, N. CompuSyn software for drug combinations and for general dose effect analysis, and user’s guide. ComboSyn, Inc. Paramus, NJ 2007. [<a href="http://www.combosyn.com" target="_blank">www.combosyn.com</a>]) which uses the method of Chou & Talalay. CI values <1, 1 and >1 indicate synergism, additive effect and antagonism, respectively.</p><p>Combination index for IFN-α and IFN-λ1 against CCHF replication respectively in A549 and HuH-7 cells.</p

Dose-dependent inhibition of CCHFV replication by recombinant IFN-α, IFN-λ1 and IFN-α+IFN-λ1.

<p>A549 <b>(a)</b> and HuH7 cells <b>(b)</b> were treated for 1 day with increasing amounts of either IFN type, alone or in combination, then infected with CCHFV at MOI 0.01; infectious virus yield was measured after overnight incubation. One out of three experiments is shown. Dotted lines: IFN-α (●) or IFN-λ1 (▲) used alone; continuous line: IFN-α and IFN-λ1 (■) used in combination.</p