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Different evolutionary pathways of HIV-1 between fetus and mother perinatal transmission pairs indicate unique immune selection in fetuses.

ABSTRACT: Study of evolution and selection pressure on HIV-1 in fetuses will lead to a better understanding of the role of immune responses in shaping virus evolution and vertical transmission. Detailed genetic analyses of HIV-1 env gene from 12 in utero transmission pairs show that most infections (67%) occur within 2 months of childbirth. In addition, the env sequences from long-term-infected fetuses are highly divergent and form separate phylogenetic lineages from their cognate maternal viruses. Host-selection sites unique to neonate viruses are identified in regions frequently targeted by neutralizing antibodies and T cell immune responses. Identification of unique selection sites in the env gene of fetal viruses indicates that the immune system in fetuses is capable of exerting selection pressure on viral evolution. Studying selection and evolution of HIV-1 or other viruses in fetuses can be an alternative approach to investigate adaptive immunity in fetuses.

SUBMITTER: Marichannegowda MH

PROVIDER: S-EPMC8324465 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Different evolutionary pathways of HIV-1 between fetus and mother perinatal transmission pairs indicate unique immune selection in fetuses.

Marichannegowda Manukumar Honnayakanahalli MH Mengual Michael M Kumar Amit A Giorgi Elena E EE Tu Joshua J JJ Martinez David R DR Romero-Severson Ethan O EO Li Xiaojun X Feng Liping L Permar Sallie R SR Gao Feng F

Cell reports. Medicine 20210616 7

Study of evolution and selection pressure on HIV-1 in fetuses will lead to a better understanding of the role of immune responses in shaping virus evolution and vertical transmission. Detailed genetic analyses of HIV-1 env gene from 12 in utero transmission pairs show that most infections (67%) occur within 2 months of childbirth. In addition, the env sequences from long-term-infected fetuses are highly divergent and form separate phylogenetic lineages from their cognate mat ...[more]

PMID: 34337555

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Project description:It has been shown that vertical transmission of the SARS-CoV-2 strain is relatively rare, and there is still limited information on the specific impact of maternal SARS-CoV-2 infection on vertical transmission. The current study focuses on a transcriptomics analysis aimed at examining differences in gene expression between placentas from mother-newborn pairs affected by COVID-19 and those from unaffected controls. Additionally, it investigates the in situ expression of molecules involved in placental inflammation. The Papa Giovanni XXIII Hospital in Bergamo, Italy, has recorded three instances of intrauterine transmission of SARS-CoV-2. The first two cases occurred early in the pandemic and involved pregnant women in their third trimester who were diagnosed with SARS-CoV-2. The third case involved an asymptomatic woman in her second trimester with a twin pregnancy, who unfortunately delivered two stillborn fetuses due to the premature rupture of membranes. Transcriptomic analysis revealed significant differences in gene expression between the placentae of COVID-19-affected mother/newborn pairs and two matched controls. The infected and control placentae were matched for gestational age. According to the Benjamani-Hochberg method, 305 genes met the criterion of an adjusted p-value of less than 0.05, and 219 genes met the criterion of less than 0.01. Up-regulated genes involved in cell signaling (e.g., CCL20, C3, MARCO) and immune response (e.g., LILRA3, CXCL10, CD48, CD86, IL1RN, IL-18R1) suggest their potential role in the inflammatory response to SARS-CoV-2. RNAscope® technology, coupled with image analysis, was utilized to quantify the surface area covered by SARS-CoV-2, ACE2, IL-1β, IL-6, IL-8, IL-10, and TNF-α on both the maternal and fetal sides of the placenta. A non-statistically significant gradient for SARS-CoV-2 was observed, with a higher surface coverage on the fetal side (2.42 ± 3.71%) compared to the maternal side (0.74 ± 1.19%) of the placenta. Although not statistically significant, the surface area covered by ACE2 mRNA was higher on the maternal side (0.02 ± 0.04%) compared to the fetal side (0.01 ± 0.01%) of the placenta. IL-6 and IL-8 were more prevalent on the fetal side (0.03 ± 0.04% and 0.06 ± 0.08%, respectively) compared to the maternal side (0.02 ± 0.01% and 0.02 ± 0.02%, respectively). The mean surface areas of IL-1β and IL-10 were found to be equal on both the fetal (0.04 ± 0.04% and 0.01 ± 0.01%, respectively) and maternal sides of the placenta (0.04 ± 0.05% and 0.01 ± 0.01%, respectively). The mean surface area of TNF-α was found to be equal on both the fetal and maternal sides of the placenta (0.02 ± 0.02% and 0.02 ± 0.02%, respectively). On the maternal side, ACE-2 and all examined interleukins, but not TNF-α, exhibited an inverse mRNA amount compared to SARS-CoV-2. On the fetal side, ACE-2, IL-6 and IL-8 were inversely correlated with SARS-CoV-2 (r = -0.3, r = -0.1 and r = -0.4, respectively), while IL-1β and IL-10 showed positive correlations (r = 0.9, p = 0.005 and r = 0.5, respectively). TNF-α exhibited a positive correlation with SARS-CoV-2 on both maternal (r = 0.4) and fetal sides (r = 0.9) of the placenta. Further research is needed to evaluate the correlation between cell signaling and immune response genes in the placenta and the vertical transmission of SARS-CoV-2. Nonetheless, the current study extends our comprehension of the molecular and immunological factors involved in SARS-CoV-2 placental infection underlying maternal-fetal transmission.

Project description:BackgroundRetention along the elimination of Mother to Child Transmission (eMTCT) cascade in Uganda remains poor as only 62.7%-69.5% are followed up to 18months. The objective of this study was to determine the rates of retention of mother-baby pairs at two levels of the eMTCT cascade (12 and 18 months) and associated factors.MethodsThis was a longitudinal analysis of 368 mother-baby pairs who were enrolled into the eMTCT program in Kaberamaido district from January 2013 to December 2018. Data was extracted from early infant diagnosis (EID) and mothers' ART registers, entered into Microsoft Excel and then exported to Stata statistical software package version 14.0 for management and analysis. Descriptive statistics such as mean and frequencies were computed at univariate level. At the bivariate level, Cox proportional hazard regression was performed to assess the level of association between the primary outcome and each independent variable, while Cox proportional hazard regression model was built at multivariate level to determine the factors independently associated with retention of mother-baby pairs in the eMTCT program.ResultsOf the 368 mothers enrolled into the study, their average age was 29.7years (SD = 6.6). Nearly two-thirds of the mothers were married/cohabiting, (n = 232, 63.0%). The 368 mother baby pairs were observed for a total time of 6340 person months, with majority, 349 (94.8%, 95%CI = 92.0-96.7) still active in eMTCT care, while 19(5.2%, 95%CI = 3.3-8.0) were lost to follow up at 12months. At 18 months, 323 (87.8%, 95%CI = 84.0-90.8) were active in eMTCT program while 45(12.2%, 95 CI = 9.2-16.0) were lost to follow up. At bivariate level, marital status, health facility level of enrolment, mothers' ART treatment supporter, and mothers' ART enrolment time were significantly associated with survival/lost to follow up (LTFU) of mother-baby pairs along the eMTCT cascade. At multivariable level, the mothers' time of ART initiation was significantly associated with survival/lost to follow up (LTFU) of mother-baby pairs at along the eMTCT cascade, with mothers-baby pairs who were initiated during the antenatal/post-natal periods having higher hazards of LTFU compared to those who initiated ART before Antenatal period (before pregnancy), aHR = 4.37(95%CI, 1.62-11.76, P = 0.003). Mother-baby pairs who were enrolled into the eMTCT program after the implementation of HIV test and treat policy (year 2017 and 2018) had higher hazards of LTFU as compared to those enrolled before the implementation of test and treat policy in Uganda (year 2013-2016), aHR = 2.22(95% CI, 1.15-4.30, P = 0.017). All the other factors had no significant association with lost to follow up and cascade completion at multivariate level.ConclusionThere was high level of retention of mother-baby pairs in the eMTCT program in Kaberamaido at 12 months, but it was suboptimal at 18months. ART initiation during the antenatal and/or post-natal period was significantly associated with suboptimal retention of mother-baby pairs along the eMTCT cascade.

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Different evolutionary pathways of HIV-1 between fetus and mother perinatal transmission pairs indicate unique immune selection in fetuses.

Publications

Different evolutionary pathways of HIV-1 between fetus and mother perinatal transmission pairs indicate unique immune selection in fetuses.

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