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1.
J Virol ; 98(2): e0189923, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38294245

RESUMEN

After Epstein-Barr virus (EBV) genome replication and encapsidation in the nucleus, nucleocapsids are translocated into the cytoplasm for subsequent tegumentation and maturation. The EBV BGLF4 kinase, which induces partial disassembly of the nuclear lamina, and the nuclear egress complex BFRF1/BFLF2 coordinately facilitate the nuclear egress of nucleocapsids. Here, we demonstrate that within EBV reactivated epithelial cells, viral capsids, tegument proteins, and glycoproteins are clustered in the juxtanuclear concave region, accompanied by redistributed cytoplasmic organelles and the cytoskeleton regulator IQ-domain GTPase-activation protein 1 (IQGAP1), close to the microtubule-organizing center (MTOC). The assembly compartment (AC) structure was diminished in BGLF4-knockdown TW01-EBV cells and BGLF4-knockout bacmid-carrying TW01 cells, suggesting that the formation of AC structure is BGLF4-dependent. Notably, glycoprotein gp350/220 was observed by confocal imaging to be distributed in the perinuclear concave region and surrounded by the endoplasmic reticulum (ER) membrane marker calnexin, indicating that the AC may be located within a globular structure derived from ER membranes, adjacent to the outer nuclear membrane. Moreover, the viral capsid protein BcLF1 and tegument protein BBLF1 were co-localized with IQGAP1 near the cytoplasmic membrane in the late stage of replication. Knockdown of IQGAP1 did not affect the AC formation but decreased virion release from both TW01-EBV and Akata+ cells, suggesting IQGAP1-mediated trafficking regulates EBV virion release. The data presented here show that BGLF4 is required for cytoskeletal rearrangement, coordination with the redistribution of cytoplasmic organelles and IQGAP1 for virus maturation, and subsequent IQGAP1-dependent virion release.IMPORTANCEEBV genome is replicated and encapsidated in the nucleus, and the resultant nucleocapsids are translocated to the cytoplasm for subsequent virion maturation. We show that a cytoplasmic AC, containing viral proteins, markers of the endoplasmic reticulum, Golgi, and endosomes, is formed in the juxtanuclear region of epithelial and B cells during EBV reactivation. The viral BGLF4 kinase contributes to the formation of the AC. The cellular protein IQGAP1 is also recruited to the AC and partially co-localizes with the virus capsid protein BcLF1 and tegument protein BBLF1 in EBV-reactivated cells, dependent on the BGLF4-induced cytoskeletal rearrangement. In addition, virion release was attenuated in IQGAP1-knockdown epithelial and B cells after reactivation, suggesting that IQGAP1-mediated trafficking may regulate the efficiency of virus maturation and release.


Asunto(s)
Citoplasma , Herpesvirus Humano 4 , Proteínas Serina-Treonina Quinasas , Proteínas Virales , Virión , Ensamble de Virus , Liberación del Virus , Proteínas Activadoras de ras GTPasa , Humanos , Proteínas de la Cápside/metabolismo , Citoplasma/metabolismo , Citoplasma/virología , Infecciones por Virus de Epstein-Barr/metabolismo , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/química , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/crecimiento & desarrollo , Herpesvirus Humano 4/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Activadoras de ras GTPasa/metabolismo , Proteínas Virales/metabolismo , Virión/química , Virión/crecimiento & desarrollo , Virión/metabolismo , Ensamble de Virus/fisiología , Retículo Endoplásmico/metabolismo , Endosomas/metabolismo , Aparato de Golgi/metabolismo
2.
BMC Infect Dis ; 23(1): 301, 2023 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-37158835

RESUMEN

BACKGROUND: Dengue virus (DENV) is the leading cause of arboviral diseases in humans worldwide. Currently Dengvaxia, the first dengue vaccine licensed in 20 countries, was recommended for DENV seropositive individuals aged 9-45 years. Studying dengue seroprevalence can improve our understanding of the epidemiology and transmission dynamics of DENV, and facilitate future intervention strategies and assessment of vaccine efficacy. Several DENV envelope protein-based serological tests including IgG and IgG-capture enzyme-linked immunosorbent assays (ELISAs) have been employed in seroprevalence studies. Previously DENV IgG-capture ELISA was reported to distinguish primary and secondary DENV infections during early convalescence, however, its performance over time and in seroprevalence study remains understudied. METHODS: In this study, we used well-documented neutralization test- or reverse-transcription-polymerase-chain reaction-confirmed serum/plasma samples including DENV-naïve, primary and secondary DENV, primary West Nile virus, primary Zika virus, and Zika with previous DENV infection panels to compare the performance of three ELISAs. RESULTS: The sensitivity of the InBios IgG ELISA was higher than that of InBios IgG-capture and SD IgG-capture ELISAs. The sensitivity of IgG-capture ELISAs was higher for secondary than primary DENV infection panel. Within the secondary DENV infection panel, the sensitivity of InBios IgG-capture ELISA decreased from 77.8% at < 6 months to 41.7% at 1-1.5 years, 28.6% at 2-15 years and 0% at > 20 years (p < 0.001, Cochran-Armitage test for trend), whereas that of IgG ELISA remains 100%. A similar trend was observed for SD IgG-capture ELISA. CONCLUSIONS: Our findings demonstrate higher sensitivity of DENV IgG ELISA than IgG-capture ELISA in seroprevalence study and interpretation of DENV IgG-capture ELISA should take sampling time and primary or secondary DENV infection into consideration.


Asunto(s)
Virus del Dengue , Infección por el Virus Zika , Virus Zika , Humanos , Estudios Seroepidemiológicos , Ensayo de Inmunoadsorción Enzimática , Pruebas de Neutralización , Inmunoglobulina G
3.
J Virol ; 94(3)2020 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-31694953

RESUMEN

Epstein-Barr virus (EBV) genomic DNA is replicated and packaged into procapsids in the nucleus to form nucleocapsids, which are then transported into the cytoplasm for tegumentation and final maturation. The process is facilitated by the coordination of the viral nuclear egress complex (NEC), which consists of BFLF2 and BFRF1. By expression alone, BFLF2 is distributed mainly in the nucleus. However, it colocalizes with BFRF1 at the nuclear rim and in cytoplasmic nuclear envelope-derived vesicles in coexpressing cells, suggesting temporal control of the interaction between BFLF2 and BFRF1 is critical for their proper function. The N-terminal sequence of BFLF2 is less conserved than that of alpha- and betaherpesvirus homologs. Here, we found that BFLF2 amino acids (aa) 2 to 102 are required for both nuclear targeting and its interaction with BFRF1. Coimmunoprecipitation and confocal analysis indicated that aa 82 to 106 of BFLF2 are important for its interaction with BFRF1. Three crucial amino acids (R47, K50, and R52) and several noncontinuous arginine and histidine residues within aa 59 to 80 function together as a noncanonical nuclear localization signal (NLS), which can be transferred onto yellow fluorescent protein (YFP)-LacZ for nuclear targeting in an importin ß-dependent manner. Virion secretion is defective in 293 cells harboring a BFLF2 knockout EBV bacmid upon lytic induction and is restored by trans-complementation of wild-type BFLF2, but not NLS or BFRF1-interacting defective mutants. In addition, multiple domains of BFRF1 were found to bind BFLF2, suggesting multiple contact regions within BFRF1 and BFLF2 are required for proper nuclear egress of EBV nucleocapsids.IMPORTANCE Although Epstein-Barr virus (EBV) BFRF1 and BFLF2 are homologs of conserved viral nuclear egress complex (NEC) in all human herpesviruses, unique amino acid sequences and functions were identified in both proteins. In this study, the nuclear targeting and BFRF1-interacting domains were found within the N terminus of BFLF2. We showed that amino acids (aa) 82 to 106 are the major region required for BFLF2 to interact with BFRF1. However, the coimmunoprecipitation (Co-IP) data and glutathione transferase (GST) pulldown experiments revealed that multiple regions of both proteins contribute to reciprocal interactions. Different from the canonical nuclear localization signal (NLS) in other herpes viral homologs, BFLF2 contains a novel importin-dependent nuclear localization signal, including R47, K50, and R52 and several neighboring discontinuous arginine and histidine residues. Using a bacmid complementation system, we show that both the nuclear targeting and the novel nuclear localization signal within aa 82 to 106 of BFLF2 are required for virion secretion.


Asunto(s)
Núcleo Celular/virología , Herpesvirus Humano 4/genética , Proteínas Virales/metabolismo , Liberación del Virus/fisiología , Secuencia de Aminoácidos , Línea Celular , Citoplasma/metabolismo , Glutatión Transferasa/metabolismo , Células HEK293 , Células HeLa , Humanos , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Modelos Moleculares , Membrana Nuclear , Señales de Localización Nuclear/metabolismo , Conformación Proteica , Análisis de Secuencia de Proteína , Proteínas Virales/química , Proteínas Virales/genética , Virión/metabolismo , Liberación del Virus/genética , beta Carioferinas
4.
J Virol ; 93(22)2019 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-31462559

RESUMEN

Hepatitis C virus (HCV) NS3 protein possesses protease and helicase activities and is considered an oncoprotein in virus-derived hepatocellular carcinoma. The NS3-associated oncogenesis has been studied but not fully understood. In this study, we have identified novel interactions of the NS3 protein with DNA repair factors, Werner syndrome protein (WRN) and Ku70, in both an HCV subgenomic replicon system and Huh7 cells expressing NS3. HCV NS3 protein inhibits WRN-mediated DNA repair and reduces the repair efficiency of nonhomologous end joining. It interferes with Ku70 recruitment to the double-strand break sites and alters the nuclear distribution of WRN-Ku repair complex. In addition, WRN is a substrate of the NS3/4A protease; the level of WRN protein is regulated by both the proteasome degradation pathway and HCV NS3/4A protease activity. The dual role of HCV NS3 and NS3/4A proteins in regulating the function and expression level of the WRN protein intensifies the effect of impairment on DNA repair. This may lead to an accumulation of DNA mutations and genome instability and, eventually, tumor development.IMPORTANCE HCV infection is a worldwide problem of public health and a major contributor to hepatocellular carcinoma. The single-stranded RNA virus with RNA-dependent RNA polymerase experiences a high error rate and develops strategies to escape the immune system and hepatocarcinogenesis. Studies have revealed the involvement of HCV proteins in the impairment of DNA repair. The present study aimed to further elucidate mechanisms by which the viral NS3 protein impairs the repair of DNA damage. Our results clearly indicate that HCV NS3/4A protease targets WRN for degradation, and, at the same time, diminishes the repair efficiency of nonhomologous end joining by interfering with the recruitment of Ku protein to the DNA double-strand break sites. The study describes a novel mechanism by which the NS3 protein influences DNA repair and provides new insight into the molecular mechanism of HCV pathogenesis.


Asunto(s)
Reparación del ADN por Unión de Extremidades , Hepacivirus/genética , Hepacivirus/metabolismo , Proteínas no Estructurales Virales/metabolismo , Helicasa del Síndrome de Werner/metabolismo , Línea Celular , ADN/metabolismo , Roturas del ADN de Doble Cadena , Daño del ADN , Reparación del ADN/fisiología , Proteínas de Unión al ADN/metabolismo , Exodesoxirribonucleasas/metabolismo , Células HEK293 , Hepatitis C Crónica/genética , Humanos , Autoantígeno Ku/genética , ARN Polimerasa Dependiente del ARN/genética , Proteínas no Estructurales Virales/genética , Helicasa del Síndrome de Werner/fisiología
6.
Int J Infect Dis ; 139: 92-100, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38056689

RESUMEN

OBJECTIVES: Chikungunya virus (CHIKV), a reemerging global public health concern, which causes acute febrile illness, rash, and arthralgia and may affect both mothers and infants during pregnancy. Mother-to-child transmission (MTCT) of CHIKV in Africa remains understudied. METHODS: Our cohort study screened 1006 pregnant women with a Zika/dengue/CHIKV rapid test at two clinics in Nigeria between 2019 and 2022. Women who tested positive for the rapid test were followed through their pregnancy and their infants were observed for 6 months, with a subset tested by reverse transcription-polymerase chain reaction (RT-PCR) and neutralization, to investigate seropositivity rates and MTCT of CHIKV. RESULTS: Of the 1006, 119 tested positive for CHIKV immunoglobulin (Ig)M, of which 36 underwent detailed laboratory tests. While none of the IgM reactive samples were RT-PCR positive, 14 symptomatic pregnant women were confirmed by CHIKV neutralization test. Twelve babies were followed with eight normal and four abnormal outcomes, including stillbirth, cleft lip/palate with microcephaly, preterm delivery, polydactyly with sepsis, and jaundice. CHIKV IgM testing identified three possible antepartum transmissions. CONCLUSION: In Nigeria, we found significant CHIKV infection in pregnancy and possible CHIKV antepartum transmission associated with birth abnormalities.


Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Labio Leporino , Fisura del Paladar , Dengue , Infección por el Virus Zika , Virus Zika , Lactante , Recién Nacido , Humanos , Femenino , Embarazo , Virus Chikungunya/genética , Mujeres Embarazadas , Estudios de Cohortes , Nigeria/epidemiología , Labio Leporino/complicaciones , Transmisión Vertical de Enfermedad Infecciosa , Fisura del Paladar/complicaciones , Fiebre Chikungunya/diagnóstico , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/complicaciones , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/epidemiología , Mortinato , Inmunoglobulina M
7.
Emerg Microbes Infect ; 13(1): 2301666, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38163752

RESUMEN

In the past few decades, several emerging/re-emerging mosquito-borne flaviviruses have resulted in disease outbreaks of public health concern in the tropics and subtropics. Due to cross-reactivities of antibodies recognizing the envelope protein of different flaviviruses, serosurveillance remains a challenge. Previously we reported that anti-premembrane (prM) antibody can discriminate between three flavivirus infections by Western blot analysis. In this study, we aimed to develop a serological assay that can discriminate infection or exposure with flaviviruses from four serocomplexes, including dengue (DENV), Zika (ZIKV), West Nile (WNV) and yellow fever (YFV) viruses, and explore its application for serosurveillance in flavivirus-endemic countries. We employed Western blot analysis including antigens of six flaviviruses (DENV1, 2 and 4, WNV, ZIKV and YFV) from four serocomplexes. We tested serum samples from YF-17D vaccinees, and from DENV, ZIKV and WNV panels that had been confirmed by RT-PCR or by neutralization assays. The overall sensitivity/specificity of anti-prM antibodies for DENV, ZIKV, WNV, and YFV infections/exposure were 91.7%/96.4%, 91.7%/99.2%, 88.9%/98.3%, and 91.3%/92.5%, respectively. When testing 48 samples from Brazil, we identified multiple flavivirus infections/exposure including DENV and ZIKV, DENV and YFV, and DENV, ZIKV and YFV. When testing 50 samples from the Philippines, we detected DENV, ZIKV, and DENV and ZIKV infections with a ZIKV seroprevalence rate of 10%, which was consistent with reports of low-level circulation of ZIKV in Asia. Together, these findings suggest that anti-prM antibody is a flavivirus serocomplex-specific marker and can be employed to delineate four flavivirus infections/exposure in regions where multiple flaviviruses co-circulate.


Asunto(s)
Virus del Dengue , Dengue , Infecciones por Flavivirus , Flavivirus , Infección por el Virus Zika , Virus Zika , Animales , Flavivirus/genética , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/epidemiología , Virus Zika/genética , Virus del Dengue/genética , Estudios Seroepidemiológicos , Anticuerpos Antivirales , Infecciones por Flavivirus/diagnóstico , Infecciones por Flavivirus/epidemiología , Virus de la Fiebre Amarilla , Reacciones Cruzadas
8.
Front Immunol ; 14: 1202055, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37554332

RESUMEN

Introduction: Dengue virus (DENV) is the leading cause of mosquito-borne viral diseases in humans. Dengvaxia, the first licensed dengue vaccine, is recommended for DENV-seropositive individuals aged 9-45 years. In the Philippines, Dengvaxia was administered to more than 830,000 children without prior serological testing in 2016-2017. Subsequently, it was revealed that DENV-seronegative children who received Dengvaxia developed severe disease following breakthrough DENV infection. As a result, thousands of children participating in the mass vaccination campaign were at higher risk of severe dengue disease. It is vital that an assay that identifies baseline DENV-naïve Dengvaxia recipients be developed and validated. This would permit more frequent and extensive assessments and timely treatment of breakthrough DENV infections. Methods: We evaluated the performance of a candidate assay, the DENV1-4 nonstructural protein 1 (NS1) IgG enzyme-linked immunosorbent assay (ELISA), developed by the University of Hawaii (UH), using well-documented serum/plasma samples including those >20 years post-DENV infection, and tested samples from 199 study participants including 100 Dengvaxia recipients from the fever surveillance programs in the Philippines. Results: The sensitivity and specificity of the assay were 96.6% and 99.4%, respectively, which are higher than those reported for pre-vaccination screening. A significantly higher rate of symptomatic breakthrough DENV infection was found among children that were DENV-naïve (10/23) than among those that were DENV-immune (7/53) when vaccinated with Dengvaxia (p=0.004, Fisher's exact test), demonstrating the feasibility of the assay and algorithms in clinical practice. Conclusion: The UH DENV1-4 NS1 IgG ELISA can determine baseline DENV serostatus among Dengvaxia recipients not only during non-acute dengue but also during breakthrough DENV infection, and has implications for assessing the long-term safety and effectiveness of Dengvaxia in the post-licensure period.


Asunto(s)
Virus del Dengue , Dengue , Niño , Animales , Humanos , Dengue/diagnóstico , Dengue/epidemiología , Filipinas/epidemiología , Anticuerpos Antivirales , Inmunoglobulina G
9.
Microbiol Spectr ; 11(4): e0408122, 2023 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-37428104

RESUMEN

Although mRNA-based COVID-19 vaccines reduce the risk of severe disease, hospitalization and death, vaccine effectiveness (VE) against infection and disease from variants of concern (VOC) wanes over time. Neutralizing antibodies (NAb) are surrogates of protection and are enhanced by a booster dose, but their kinetics and durability remain understudied. Current recommendation of a booster dose does not consider the existing NAb in each individual. Here, we investigated 50% neutralization (NT50) titers against VOC among COVID-19-naive participants receiving the Moderna (n = 26) or Pfizer (n = 25) vaccine for up to 7 months following the second dose, and determined their half-lives. We found that the time it took for NT50 titers to decline to 24, equivalent to 50% inhibitory dilution of 10 international units/mL, was longer in the Moderna (325/324/235/274 days for the D614G/alpha/beta/delta variants) group than in the Pfizer (253/252/174/226 days) group, which may account for the slower decline in VE of the Moderna vaccine observed in real-world settings and supports our hypothesis that measuring the NT50 titers against VOC, together with information on NAb half-lives, can be used to dictate the time of booster vaccination. Our study provides a framework to determine the optimal time of a booster dose against VOC at the individual level. In response to future VOC with high morbidity and mortality, a quick evaluation of NAb half-lives using longitudinal serum samples from clinical trials or research programs of different primary-series vaccinations and/or one or two boosters could provide references for determining the time of booster in different individuals. IMPORTANCE Despite improved understanding of the biology of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the evolutionary trajectory of the virus is uncertain, and the concern of future antigenically distinct variants remains. Current recommendations for a COVID-19 vaccine booster dose are primarily based on neutralization capacity, effectiveness against circulating variants of concern (VOC), and other host factors. We hypothesized that measuring neutralizing antibody titers against SARS-CoV-2 VOC together with half-life information can be used to dictate the time of booster vaccination. Through detailed analysis of neutralizing antibodies against VOC among COVID-19-naive vaccinees receiving either of two mRNA vaccines, we found that the time it took for 50% neutralization titers to decline to a reference level of protection was longer in the Moderna than in the Pfizer group, which supports our hypothesis. In response to future VOC with potentially high morbidity and mortality, our proof-of-concept study provides a framework to determine the optimal time of a booster dose at the individual level.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , Semivida , SARS-CoV-2/genética , COVID-19/prevención & control , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunación
10.
medRxiv ; 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37808865

RESUMEN

In the past few decades, several emerging/re-emerging mosquito-borne flaviviruses have resulted in disease outbreaks of public health concern in the tropics and subtropics. Due to cross-reactivities of antibodies recognizing the envelope protein of different flaviviruses, serosurveillance remains a challenge. Previously we reported that anti-premembrane (prM) antibody can discriminate between three flavivirus infections by Western blot analysis. In this study, we aimed to develop a serological assay that can discriminate infection or exposure with flaviviruses from four serocomplexes, including dengue (DENV), Zika (ZIKV), West Nile (WNV) and yellow fever (YFV) viruses, and explore its application for serosurveillance in flavivirus-endemic countries. We employed Western blot analysis including antigens of six flaviviruses (DENV1, 2 and 4, WNV, ZIKV and YFV) from four serocomplexes. We tested serum samples from YF-17D vaccinees, and from DENV, ZIKV and WNV panels that had been confirmed by RT-PCR or by neutralization assays. The overall sensitivity/specificity of anti-prM antibodies for DENV, ZIKV, WNV, and YFV infections/exposure were 91.7%/96.4%, 91.7%/99.2%, 88.9%/98.3%, and 91.3%/92.5%, respectively. When testing 48 samples from Brazil, we identified multiple flavivirus infections/exposure including DENV and ZIKV, DENV and YFV, and DENV, ZIKV and YFV. When testing 50 samples from the Philippines, we detected DENV, ZIKV, and DENV and ZIKV infections with a ZIKV seroprevalence rate of 10%, which was consistent with reports of low-level circulation of ZIKV in Asia. Together, these findings suggest that anti-prM antibody is a flavivirus serocomplex-specific marker and can be employed to delineate four flavivirus infections/exposure in regions where multiple flaviviruses co-circulate.

11.
medRxiv ; 2023 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-37609234

RESUMEN

The adverse impact of Zika (ZIKV), dengue (DENV), and chikungunya (CHIKV) virus infection in pregnancy has been recognized in Latin America and Asia but is not well studied in Africa. In Nigeria, we screened 1006 pregnant women for ZIKV, DENV and CHIKV IgM/IgG by rapid test (2019-2022). Women with acute infection were recruited for prospective study and infants were examined for any abnormalities from delivery through six months. A subset of rapid test-reactive samples were confirmed using virus-specific ELISAs and neutralization assays. Prevalence of acute infection (IgM+) was 3.8%, 9.9% and 11.8% for ZIKV, DENV and CHIKV, respectively; co-infections represented 24.5% of all infections. Prevalence in asymptomatic women was twice the level of symptomatic infection. We found a significant association between acute maternal ZIKV/DENV/CHIKV infection and any gross abnormal birth outcome (p=0.014). Further prospective studies will contribute to our understanding of the clinical significance of these endemic arboviruses in Africa.

12.
medRxiv ; 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37609297

RESUMEN

Chikungunya virus (CHIKV) has become a global public health concern since the reemergence of the Indian Ocean lineage and expansion of the Asian genotype. CHIKV infection causes acute febrile illness, rash, and arthralgia and during pregnancy may affect both mothers and infants. The mother-to-child transmission (MTCT) of CHIKV in Africa remains understudied. We screened 1006 pregnant women at two clinics in Nigeria between 2019 and 2022 and investigated the prevalence and MTCT of CHIKV. Of the 1006, 119 tested positive for CHIKV IgM, of which 36 underwent detailed laboratory tests. While none of the IgM reactive samples were RT-PCR positive, 14 symptomatic pregnant women were confirmed by CHIKV neutralization test. Twelve babies were followed with 8 normal and 4 abnormal outcomes, including stillbirth, cleft lip/palate with microcephaly, preterm delivery, polydactyly with sepsis and jaundice. CHIKV IgM testing identified 3 antepartum transmissions, further studies will determine its impact in antepartum infection.

13.
J Clin Virol ; 169: 105616, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37944259

RESUMEN

BACKGROUND: The adverse impact of Zika (ZIKV), dengue (DENV), and chikungunya (CHIKV) virus infection in pregnancy has been recognized in Latin America and Asia but is not well studied in Africa. Although originally discovered in sub-Saharan Africa the non-specific clinical presentation of arbovirus infection may have hampered our detection of adverse clinical outcomes and outbreak. OBJECTIVE: This prospective study of arbovirus infection in pregnant women in north-central Nigeria sought to characterize the prevalence of acute arbovirus infection and determine the impact on pregnancy and infant outcomes. METHODS: In Nigeria, we screened 1006 pregnant women for ZIKV, DENV and CHIKV IgM/IgG by rapid test (2019-2022). Women with acute infection were recruited for prospective study and infants were examined for any abnormalities from delivery through six months. A subset of rapid test-reactive samples were confirmed using virus-specific ELISAs and neutralization assays. RESULTS: The prevalence of acute infection (IgM+) was 3.8 %, 9.9 % and 11.8 % for ZIKV, DENV and CHIKV, respectively; co-infections represented 24.5 % of all infections. The prevalence in asymptomatic women was twice the level of symptomatic infection. We found a significant association between acute maternal ZIKV/DENV/CHIKV infection and any gross abnormal birth outcome (p = 0.014). CONCLUSIONS: Over three rainy seasons, regular acute infection with ZIKV, DENV, and CHIKV was observed with significantly higher rates in pregnant women without symptoms. The potential association arbovirus infection with abnormal birth outcome warrants further prospective study to ascertain the clinical significance of these endemic arboviruses in Africa.


Asunto(s)
Infecciones por Arbovirus , Arbovirus , Fiebre Chikungunya , Virus Chikungunya , Virus del Dengue , Dengue , Infección por el Virus Zika , Virus Zika , Lactante , Humanos , Femenino , Embarazo , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/diagnóstico , Dengue/diagnóstico , Mujeres Embarazadas , Estudios Prospectivos , Nigeria/epidemiología , Fiebre Chikungunya/diagnóstico , Infecciones por Arbovirus/epidemiología , Inmunoglobulina M
14.
Front Med (Lausanne) ; 9: 1019490, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36523785

RESUMEN

Uncontrolled transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence of several variants of concern (VOC). As vaccine-induced neutralizing antibodies against VOC waned over time, breakthrough infections (BTIs) have been reported primarily among healthcare workers or in long-term care facilities. Most BTIs were identified by reverse transcription-polymerase chain reaction (RT-PCR) or antigen test for individuals experiencing symptoms, known as symptomatic BTIs. In this study, we detected seroconversion of anti-nucleocapsid (N) antibody to identify both symptomatic and asymptomatic BTIs in a cohort of COVID-19-naive university employees and students following two or three doses of mRNA vaccines. We reported 4 BTIs among 85 (4.7%) participants caused by the Omicron and Delta VOC during the transition from the Delta to Omicron wave of the pandemic; three were symptomatic and confirmed by RT-PCR test and one asymptomatic. A symptomatic reinfection two and half months after a BTI was found in one participant. Two of three symptomatic BTIs and the reinfection were confirmed by whole genome sequencing. All were supported by a >4-fold increase in neutralizing antibodies against the Delta or Omicron variant. Moreover, we found both symptomatic and asymptomatic BTIs can boost neutralizing antibodies against VOC with variable degrees ranging from 2.5- to 77.4-fold increase in neutralizing antibody titers. As BTIs continue, our findings highlight the application of anti-N antibody test to ongoing studies of immunity induced by spike-based vaccine, and provide new insights into the establishment of herd immunity in the community during the post-vaccination era.

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