Kangaroo endogenous retrovirus (KERV) forms megasatellite DNA with a simple repetition pattern in which the provirus structure is retained.

The kangaroo endogenous retrovirus (KERV) was previously reported to have undergone a rapid copy number increase in the red-necked wallaby; however, the mode of amplification was left to be clarified. The present study revealed that the long terminal repeat (LTR) (0.6 kb) and internal region (2.0 kb) of a provirus are repeated alternately, forming megasatellite DNA which we named kervRep. This repetition pattern was the same as that observed for walbRep, megasatellite DNA originating from another endogenous retrovirus. Their formation process can be explained using a simple model: pairing slippage followed by homologous recombination. This model features that the initial step is triggered by the presence of two identical sequences within a short distance; the possession of LTRs by endogenous retroviruses fulfills this condition. The discovery of two cases suggests that formation of this type of satellite DNA is one of non-negligible effects of endogenous retroviruses on their host genomes.

Recent insights into crosstalk between genetic parasites and their host genome.

The bulk of higher order organismal genomes is comprised of transposable element (TE) copies, i.e. genetic parasites. The host-parasite relation is multi-faceted, varying across genomic region (genic versus intergenic), life-cycle stages, tissue-type and of course in health versus pathological state. The reach of functional genomics though, in investigating genotype-to-phenotype relations, has been limited when TEs are involved. The aim of this review is to highlight recent progress made in understanding how TE origin biochemical activity interacts with the central dogma stages of the host genome. Such interaction can also bring about modulation of the immune context and this could have important repercussions in disease state where immunity has a role to play. Thus, the review is to instigate ideas and action points around identifying evolutionary adaptations that the host genome and the genetic parasite have evolved and why they could be relevant.

Epigenetic targeting of transposon relics: beating the dead horses of the genome?

Transposable elements (TEs) have been seen as selfish genetic elements that can propagate in a host genome. Their propagation success is however hindered by a combination of mechanisms such as mutations, selection, and their epigenetic silencing by the host genome. As a result, most copies of TEs in a given genome are dead relics: their sequence is too degenerated to allow any transposition. Nevertheless, these TE relics often, but not always, remain epigenetically silenced, and if not to prevent transposition anymore, one can wonder the reason for this phenomenon. The mere self-perpetuating loop inherent to epigenetic silencing could alone explain that even when inactive, TE copies remain silenced. Beyond this process, nevertheless, antagonistic selective forces are likely to act on TE relic silencing. Especially, without the benefit of preventing transposition, TE relic silencing may prove deleterious to the host fitness, suggesting that the maintenance of TE relic silencing is the result of a fine, and perhaps case-by-case, evolutionary trade-off between beneficial and deleterious effects. Ultimately, the release of TE relics silencing may provide a 'safe' ground for adaptive epimutations to arise. In this review, we provide an overview of these questions in both plants and animals.

Host-Genome Similarity Characterizes the Adaption of SARS-CoV-2 to Humans.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a high mutation rate and many variants have emerged in the last 2 years, including Alpha, Beta, Delta, Gamma and Omicron. Studies showed that the host-genome similarity (HGS) of SARS-CoV-2 is higher than SARS-CoV and the HGS of open reading frame (ORF) in coronavirus genome is closely related to suppression of innate immunity. Many works have shown that ORF 6 and ORF 8 of SARS-CoV-2 play an important role in suppressing IFN-ß signaling pathway in vivo. However, the relation between HGS and the adaption of SARS-CoV-2 variants is still not clear. This work investigates HGS of SARS-CoV-2 variants based on a dataset containing more than 40,000 viral genomes. The relation between HGS of viral ORFs and the suppression of antivirus response is studied. The results show that ORF 7b, ORF 6 and ORF 8 are the top 3 genes with the highest HGS. In the past 2 years, the HGS values of ORF 8 and ORF 7B of SARS-CoV-2 have increased greatly. A remarkable correlation is discovered between HGS and inhibition of antivirus response of immune system, which suggests that the similarity between coronavirus and host gnome may be an indicator of the suppression of innate immunity. Among the five variants (Alpha, Beta, Delta, Gamma and Omicron), Delta has the highest HGS and Omicron has the lowest HGS. This finding implies that the high HGS in Delta variant may indicate further suppression of host innate immunity. However, the relatively low HGS of Omicron is still a puzzle. By comparing the mutations in genomes of Alpha, Delta and Omicron variants, a commonly shared mutation ACT > ATT is identified in high-HGS strain populations. The high HGS mutations among the three variants are quite different. This finding strongly suggests that mutations in high HGS strains are different in different variants. Only a few common mutations survive, which may play important role in improving the adaptability of SARS-CoV-2. However, the mechanism for how the mutations help SARS-CoV-2 escape immunity is still unclear. HGS analysis is a new method to study virus−host interaction and may provide a way to understand the rapid mutation and adaption of SARS-CoV-2.

Interplay between Genome, Metabolome and Microbiome in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC), a major health concern, is developed depending on environmental, genetic and microbial factors. The microbiome and metabolome have been analyzed to study their role in CRC. However, the interplay of host genetics with those layers in CRC remains unclear. METHODS: 120 individuals were sequenced and association analyses were carried out for adenoma and CRC risk, and for selected components of the microbiome and metabolome. The epistasis between genes located in cholesterol pathways was analyzed; modifiable risk factors were studied using Mendelian randomization; and the three omic layers were used to integrate their data and to build risk prediction models. RESULTS: We detected genetic variants that were associated to components of metabolome or microbiome and adenoma or CRC risk (e.g., in LINC01605, PROKR2 and CCSER1 genes). In addition, we found interactions between genes of cholesterol metabolism, and HDL cholesterol levels affected adenoma (p = 0.0448) and CRC (p = 0.0148) risk. The combination of the three omic layers to build risk prediction models reached high AUC values (>0.91). CONCLUSIONS: The use of the three omic layers allowed for the finding of biological mechanisms related to the development of adenoma and CRC, and each layer provided complementary information to build risk prediction models.

Transcriptionally inactive hepatitis B virus episome DNA preferentially resides in the vicinity of chromosome 19 in 3D host genome upon infection.

The hepatitis B virus (HBV) infects 257 million people worldwide. HBV infection requires establishment and persistence of covalently closed circular (ccc) DNA, a viral episome, in nucleus. Here, we study cccDNA spatial localization in the 3D host genome by using chromosome conformation capture-based sequencing analysis and fluorescence in situ hybridization (FISH). We show that transcriptionally inactive cccDNA is not randomly distributed in host nucleus. Rather, it is preferentially accumulated at specialized areas, including regions close to chromosome 19 (chr.19). Activation of the cccDNA is apparently associated with its re-localization, from a pre-established heterochromatin hub formed by 5 regions of chr.19 to transcriptionally active regions formed by chr.19 and nearby chromosomes including chr.16, 17, 20, and 22. This active versus inactive positioning at discrete regions of the host genome is primarily controlled by the viral HBx protein and by host factors including the structural maintenance of chromosomes protein 5/6 (SMC5/6) complex.

Shorter androgen receptor polyQ alleles protect against life-threatening COVID-19 disease in European males.

BACKGROUND: While SARS-CoV-2 similarly infects men and women, COVID-19 outcome is less favorable in men. Variability in COVID-19 severity may be explained by differences in the host genome. METHODS: We compared poly-amino acids variability from WES data in severely affected COVID-19 patients versus SARS-CoV-2 PCR-positive oligo-asymptomatic subjects. FINDINGS: Shorter polyQ alleles (≤22) in the androgen receptor (AR) conferred protection against severe outcome in COVID-19 in the first tested cohort (both males and females) of 638 Italian subjects. The association between long polyQ alleles (≥23) and severe clinical outcome (p = 0.024) was also validated in an independent cohort of Spanish men <60 years of age (p = 0.014). Testosterone was higher in subjects with AR long-polyQ, possibly indicating receptor resistance (p = 0.042 Mann-Whitney U test). Inappropriately low serum testosterone level among carriers of the long-polyQ alleles (p = 0.0004 Mann-Whitney U test) predicted the need for intensive care in COVID-19 infected men. In agreement with the known anti-inflammatory action of testosterone, patients with long-polyQ and age ≥60 years had increased levels of CRP (p = 0.018, not accounting for multiple testing). INTERPRETATION: We identify the first genetic polymorphism that appears to predispose some men to develop more severe disease. Failure of the endocrine feedback to overcome AR signaling defects by increasing testosterone levels during the infection leads to the polyQ tract becoming dominant to serum testosterone levels for the clinical outcome. These results may contribute to designing reliable clinical and public health measures and provide a rationale to test testosterone as adjuvant therapy in men with COVID-19 expressing long AR polyQ repeats. FUNDING: MIUR project "Dipartimenti di Eccellenza 2018-2020" to Department of Medical Biotechnologies University of Siena, Italy (Italian D.L. n.18 March 17, 2020) and "Bando Ricerca COVID-19 Toscana" project to Azienda Ospedaliero-Universitaria Senese. Private donors for COVID-19 research and charity funds from Intesa San Paolo.

A SARS-CoV-2 host infection model network based on genomic human Transcription Factors (TFs) depletion.

In December 2019 a new beta-coronavirus was isolated and characterized by sequencing samples from pneumonia patients in Wuhan, Hubei Province, China. Coronaviruses are positive-sense RNA viruses widely distributed among different animal species and humans in which they cause respiratory, enteric, liver and neurological symptomatology. Six species of coronavirus have been described (HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1) that cause cold-like symptoms in immunocompetent or immunocompromised subjects and two strains of sometimes fatal zoonotic origin that cause severe acute respiratory syndrome (SARS-CoV and MERS-CoV). The SARS-CoV-2 strain is the emerging seventh member of the coronavirus family, which is actually determining a global emergency. In silico analysis is a promising approach for understanding biological events in complex diseases and due to serious worldwide emergency and serious threat to global health, it is extremely important to use bioinformatics methods able to study an emerging pathogen like SARS-CoV-2. Herein, we report on in silico comparative analysis between complete genome of SARS-CoV, MERS-CoV, HCoV-OC43 and SARS-CoV-2 strains, to identify the occurrence of specific conserved motifs on viral genomic sequences which should be able to bind and therefore induce a subtraction of host's Transcription Factors (TFs) which lead to a depletion, an effect comparable to haploinsufficiency (a genetic dominant condition in which a single copy of wild-type allele at a locus, in heterozygous combination with a variant allele, is insufficient to produce the correct quantity of transcript and, therefore, of protein, for a correct standard phenotypic expression). In this competitive scenario, virus versus host, the proposed in silico protocol identified the TFs same as the distribution of TFBSs (Transcription Factor Binding Sites) on analyzed viral strains, potentially able to influence genes and pathways with biological functions confirming that this approach could brings useful insights regarding SARS-CoV-2. According to our results obtained by this in silico approach it is possible to hypothesize that TF-binding motifs could be of help in the explanation of the complex and heterogeneous clinical presentation in SARS-CoV-2 and subsequently predict possible interactions regarding metabolic pathways, and drug or target relationships.

Analysis of RNA sequences of 3636 SARS-CoV-2 collected from 55 countries reveals selective sweep of one virus type.

BACKGROUND & OBJECTIVES: SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) is evolving with the progression of the pandemic. This study was aimed to investigate the diversity and evolution of the coronavirus SARS-CoV-2 with progression of the pandemic over time and to identify similarities and differences of viral diversity and evolution across geographical regions (countries). METHODS: Publicly available data on type definitions based on whole-genome sequences of the SARS-CoV-2 sampled during December and March 2020 from 3636 infected patients spread over 55 countries were collected. Phylodynamic analyses were performed and the temporal and spatial evolution of the virus was examined. RESULTS: It was found that (i) temporal variation in frequencies of types of the coronavirus was significant; ancestral viruses of type O were replaced by evolved viruses belonging to type A2a; (ii) spatial variation was not significant; with the spread of SARS-CoV-2, the dominant virus was the A2a type virus in every geographical region; (iii) within a geographical region, there was significant micro-level variation in the frequencies of the different viral types, and (iv) the evolved coronavirus of type A2a swept rapidly across all continents. INTERPRETATION & CONCLUSIONS: SARS-CoV-2 belonging to the A2a type possesses a non-synomymous variant (D614G) that possibly eases the entry of the virus into the lung cells of the host. This may be the reason why the A2a type has an advantage to infect and survive and as a result has rapidly swept all geographical regions. Therefore, large-scale sequencing of coronavirus genomes and, as required, of host genomes should be undertaken in India to identify regional and ethnic variation in viral composition and its interaction with host genomes. Further, careful collection of clinical and immunological data of the host can provide deep learning in relation to infection and transmission of the types of coronavirus genomes.

An Information-Based Approach for Mediation Analysis on High-Dimensional Metagenomic Data.

The human microbiome plays a critical role in the development of gut-related illnesses such as inflammatory bowel disease and clinical pouchitis. A mediation model can be used to describe the interaction between host gene expression, the gut microbiome, and clinical/health situation (e.g., diseased or not, inflammation level) and may provide insights into underlying disease mechanisms. Current mediation regression methodology cannot adequately model high-dimensional exposures and mediators or mixed data types. Additionally, regression based mediation models require some assumptions for the model parameters, and the relationships are usually assumed to be linear and additive. With the microbiome being the mediators, these assumptions are violated. We propose two novel nonparametric procedures utilizing information theory to detect significant mediation effects with high-dimensional exposures and mediators and varying data types while avoiding standard regression assumptions. Compared with available methods through comprehensive simulation studies, the proposed method shows higher power and lower error. The innovative method is applied to clinical pouchitis data as well and interesting results are obtained.

Whole-Genome Analysis of Domestic Chicken Selection Lines Suggests Segregating Variation in ERV Makeups.

Retroviruses have invaded vertebrate hosts for millions of years and left an extensive endogenous retrovirus (ERV) record in the host genomes, which provides a remarkable source for an evolutionary perspective on retrovirus-host associations. Here we identified ERV variation across whole-genomes from two chicken lines, derived from a common founder population subjected to 50 years of bi-directional selection on body weight, and a distantly related domestic chicken line as a comparison outgroup. Candidate ERV loci, where at least one of the chicken lines indicated distinct differences, were analyzed for adjacent host genomic landscapes, selective sweeps, and compared by sequence associations to reference assembly ERVs in phylogenetic analyses. Current data does not support selection acting on specific ERV loci in the domestic chicken lines, as determined by presence inside selective sweeps or composition of adjacent host genes. The varying ERV records among the domestic chicken lines associated broadly across the assembly ERV phylogeny, indicating that the observed insertion differences result from pre-existing and segregating ERV loci in the host populations. Thus, data suggest that the observed differences between the host lineages are best explained by substantial standing ERV variation within host populations, and indicates that even truncated, presumably old, ERVs have not yet become fixed in the host population.

Human Papillomavirus 16 E2 Regulates Keratinocyte Gene Expression Relevant to Cancer and the Viral Life Cycle.

Human papillomaviruses (HPVs) are causative agents in ano-genital and oropharyngeal cancers. The virus must reprogram host gene expression to promote infection, and E6 and E7 contribute to this via the targeting of cellular transcription factors, including p53 and pRb, respectively. The HPV16 E2 protein regulates host gene expression in U2OS cells, and in this study, we extend these observations into telomerase reverse transcriptase (TERT) immortalized oral keratinocytes (NOKs) that are capable of supporting late stages of the HPV16 life cycle. We observed repression of innate immune genes by E2 that are also repressed by the intact HPV16 genome in NOKs. Transcriptome sequencing (RNA-seq) data identified 167 up- and 395 downregulated genes by E2; there was a highly significant overlap of the E2-regulated genes with those regulated by the intact HPV16 genome in the same cell type. Small interfering RNA (siRNA) targeting of E2 reversed the repression of E2-targeted genes. The ability of E2 to repress innate immune genes was confirmed in an ano-genital immortalized keratinocyte cell line, N/Tert-1. We present the analysis of data from The Cancer Genome Atlas (TCGA) for HPV16-positive and -negative head and neck cancers (HNC) suggesting that E2 plays a role in the regulation of the host genome in cancers. Patients with HPV16-positive HNC with a loss of E2 expression exhibited a worse clinical outcome, and we discuss how this could, at least partially, be related to the loss of E2 host gene regulation.IMPORTANCE Human papillomavirus 16 (HPV16)-positive tumors that retain expression of E2 have a better clinical outcome than those that have lost E2 expression. It has been suggested that this is due to a loss of E2 repression of E6 and E7 expression, but this is not supported by data from tumors where there is not more E6 and E7 expression in the absence of E2. Here we report that E2 regulates host gene expression and place this regulation in the context of the HPV16 life cycle and HPV16-positive head and neck cancers (the majority of which retain E2 expression). We propose that this E2 function may play an important part in the increased response of HPV16-positive cancers to radiation therapy. Therefore, host gene regulation by E2 may be important for promotion of the HPV16 life cycle and also for the response of HPV16-positive tumors to radiation therapy.

Gut microbiota changes in the extreme decades of human life: a focus on centenarians.

The gut microbiota (GM) is a complex, evolutionarily molded ecological system, which contributes to a variety of physiological functions. The GM is highly dynamic, being sensitive to environmental stimuli, and its composition changes over the host's entire lifespan. However, the basic question of how much these changes may be ascribed to variables such as population, diet, genetics and gender, and/or to the aging process per se is still largely unanswered. We argue that comparison among studies on centenarians-the best model of healthy aging and longevity-recruited from different geographical areas/populations (different genetics and dietary habits) can help to disentangle the contribution of aging and non-aging-related variables to GM remodeling with age. The current review focuses on the role of population, gender and host genetics as possible drivers of GM modification along the human aging process. The feedback impact of age-associated GM variation on the GM-brain axis and GM metabolomics is also discussed. We likewise address the role of GM in neurodegenerative diseases such as Parkinson's and Alzheimer's, and its possible therapeutic use, taking advantage of the fact that centenarians are characterized by an extreme (healthy) phenotype versus patients suffering from age-related pathologies. Finally, it is argued that longitudinal studies combining metagenomics sequencing and in-depth phylogenetic analysis with a comprehensive phenotypic characterization of centenarians and patients using up-to-date omics (metabolomics, transcriptomics and meta-transcriptomics) are urgently needed.

Influence of IL-6, IL-8, and TGF-β 1 gene polymorphisms on the risk of human papillomavirus-infection in women from Pernambuco, Brazil

Human papillomavirus (HPV) infections are strongly associated with the development of cervical intraepithelial neoplasias and invasive cervical cancer. Polymorphisms in cytokine-encoding genes and behavioural cofactors could play an important role in protecting an individual against viral infections and cancer. Here, we investigated whether IL-6 -174 G>C, IL-8 +396 G>T, and TGF-β1 +869 G>C and +915 G>C polymorphisms were associated with susceptibility to HPV infection in women from north-east (Pernambuco) Brazil. We analysed 108 healthy uninfected women (HC) and 108 HPV-positive women with cervical lesions. Genetic polymorphisms were assessed using Sanger sequencing and polymerase chain reaction-restriction fragment length polymorphism. Comparison of the distribution of the genotypic and allelic frequencies of the IL-18 +396 T>G polymorphism between HPV infected woman an uninfected controls showed that the GG genotype and G allele were both more frequent in the HC group, and were associated with protection from HPV infection (p = 0.0015; OR = 0.29 CI95% = 0.13-0.61; p = 0.0005; OR = 0.45 CI95% 0.29-0.7, respectively). Individuals from the control group could have previously had HPV infection that was spontaneously eliminated; however, it was undetectable at the time of sample collection. Based on our findings, we hypothesize that the IL-8 +396 G>T polymorphism could interfere with susceptibility to HPV infection, by modulating the ability of immune system to fight the virus.

VirusTAP: Viral Genome-Targeted Assembly Pipeline.

Although next-generation sequencing (NGS) technology provides a comprehensive means with which to identify potential pathogens from clinical specimens, simple and user-friendly bioinformatics pipelines are expected to obtain the entire viral genome sequence, subsequently providing traceability, based on extensive molecular phylogenetic analyses. We have developed a web-based integrated NGS analysis tool for the viral genome (virus genome-targeted assembly pipeline: VirusTAP), which includes extensive sequence subtraction of host- or bacteria-related NGS reads prior to de novo assembly, leading to the prompt and accurate assembly of viral genome sequences from metagenomic NGS reads. The VirusTAP web site is at https://gph.niid.go.jp/cgi-bin/virustap/index.cgi/.

How did hepatitis B virus effect the host genome in the last decade?

The principal reason of chronic liver disease, cirrhosis and hepatocellular carcinoma is chronic viral hepatitis all over the world. Hepatitis B virus (HBV) has some mutagenic effects on the host genome. HBV may be exhibiting these mutagenic effects through integrating into the host genome, through its viral proteins or through some epigenetic mechanisms related with HBV proteins. This review aims to summarize the molecular mechanisms used by HBV for effecting host genome determined in the last decade. The focus will be on the effects of integration, HBV proteins, especially HBV X protein and epigenetic mechanisms on the host genome. These interactions between HBV and the host genome also forms the underlying mechanisms of the evolution of hepatocellular carcinoma.

Regulation of human genome expression and RNA splicing by human papillomavirus 16 E2 protein.

Human papillomavirus 16 (HPV16) is causative in human cancer. The E2 protein regulates transcription from and replication of the viral genome; the role of E2 in regulating the host genome has been less well studied. We have expressed HPV16 E2 (E2) stably in U2OS cells; these cells tolerate E2 expression well and gene expression analysis identified 74 genes showing differential expression specific to E2. Analysis of published gene expression data sets during cervical cancer progression identified 20 of the genes as being altered in a similar direction as the E2 specific genes. In addition, E2 altered the splicing of many genes implicated in cancer and cell motility. The E2 expressing cells showed no alteration in cell growth but were altered in cell motility, consistent with the E2 induced altered splicing predicted to affect this cellular function. The results present a model system for investigating E2 regulation of the host genome.

Host genomic HIV restriction factors modulate the response to dendritic cell-based treatment against HIV-1.

Host genome is still poorly investigated in the context of vaccine or immunotherapy, however recently findings emphasized that it may affect the response to those treatments. In our retrospective study we evaluated the effect of HIV-1 genetic restriction factors on the response to dendritic cell (DC)-based immunotherapy in a Brazilian cohort of HIV positive (HIV+) patients that underwent a phase I clinical trial in 2004. Genomic DNA from 18 HIV+ individuals that underwent DC-based immunotherapy was analyzed for selected polymorphisms known to be associated with susceptibility to HIV-1 infection and/or AIDS progression. Allelic and genotypic distribution of the 22 polymorphisms was evaluated considering the response to the treatment. The rs11884476 SNP in PARD3B resulted associated with good response to immune treatment according to an over-dominant model. Even if functional effect of this variation is still unknown, our data suggested that it could play a role in the control of viral replication. Our findings, being aware of the limitation represented by the small number of subjects analyzed, suggest that genetic factors involved in AIDS progression could affect the response to immunotherapy, reinforcing the idea that deeper investigation on host genetic variations will be fundamental for a rational vaccine development.

Role of epigenetic reprogramming of host genes in bacterial pathogenesis.

The genomes are regularly targeted by epigenetic regulatory mechanisms (DNA methylation, histone modifications, binding of regulatory proteins) in infected cells. In addition, proteins encoded by microbial genomes may disturb the action of a set of cellular promoters by interacting with the same epi-regulatory machinery. The outcome of this may result in epigenetic dysregulation and subsequent cellular dysfunctions that may manifest in or contribute to the development of pathological changes. How epigenetic methylation decorations on DNA and histones are started and established remains largely unknown. The inherited nature of these processes in regulation of genes suggests that they could play key roles in chronic diseases associated with microbial persistence; they might also explain so-called hit-and-run phenomena in infectious disease pathogenesis. Microbes infecting mammals may cause diseases by causing hyper-methylation of key cellular promoters at CpG di-nucleotides and may induce pathological changes by epigenetic reprogramming of host cells they are interacting with elucidation of the epigenetic consequences of microbe-host interactions may have important therapeutic implications because epigenetic processes can be reverted and elimination of microbes inducing patho-epigenetic changes may prevent disease development.

HIV mother-to-child transmission: a complex genetic puzzle tackled by Brazil and Argentina research teams.

Human immunodeficiency virus (HIV) mother-to-child transmission is a complex event, depending upon environmental factors and is affected by host genetic factors from mother and child, as well as viral genetic elements. The integration of multiple parameters (CD4 cell count, virus load, HIV subtype, and host genetic markers) could account for the susceptibility to HIV infection, a multifactorial trait. The goal of this manuscript is to analyze the immunogenetic factors associated to HIV mother-to-child transmission, trying to unravel the genetic puzzle of HIV mother-to-child transmission and considering the experience in this topic of two research groups from Brazil and Argentina.