HIV-associated gut microbial alterations are dependent on host and geographic context

HIV-associated changes in intestinal microbiota are believed to be important drivers of disease progression. However, the majority of studies have focused on populations in high-income countries rather than in developing regions where HIV burden is greatest. To better understand the impact of HIV on fecal microbiota globally, we compare the fecal microbial community of individuals in the U.S., Uganda, and Botswana. We identify significant bacterial taxa alterations with both treated and untreated HIV infection with a high degree of uniqueness in each cohort. HIV-associated taxa alterations are also significantly different between populations that report men who have sex with men (MSM) behavior and non-MSM populations. Additionally, while we find that HIV infection is consistently associated with higher soluble markers of immune activation, most specific bacterial taxa associated with these markers in each region are not shared and none are shared across all three geographic locations in our study. Our findings demonstrate that HIV-associated changes in fecal microbiota are overall distinct among geographical locations and sexual behavior groups, although a small number of taxa shared between pairs of geographic locations warrant further investigation, highlighting the importance of considering host context to fully assess the impact of the gut microbiome on human health and disease

Impact of the bacterial nasopharyngeal microbiota on the severity of genus enterovirus lower respiratory tract infection in children: A case-control study

Introduction: Rhinoviruses (RV) and enteroviruses (EV) are among the main causative etiologies of lower respiratory tract infection (LRTI) in children. The clinical spectrum of RV/EV infection is wide, which could be explained by diverse environmental, pathogen-, and host-related factors. Little is known about the nasopharyngeal microbiota as a risk factor or disease modifier for RV/EV infection in pediatric patients. This study describes distinct nasopharyngeal microbiota profiles according to RV/EV LRTI status in children. Methods: Cross-sectional case-control study, conducted at Hospital Sant de Déu (Barcelona, Spain) from 2017 to 2020. Three groups of children <5 years were included: healthy controls without viral detection (Group A), mild or asymptomatic controls with RV/EV infection (Group B), and cases with severe RV/EV infection admitted to the pediatric intensive care unit (PICU) (Group C). Nasopharyngeal samples were collected from participants for viral DNA/RNA detection by multiplex-polymerase chain reaction and bacterial microbiota characterization by 16S rRNA gene sequencing. Results: A total of 104 subjects were recruited (A = 17, B = 34, C = 53). Children's nasopharyngeal microbiota composition varied according to their RV/EV infection status. Richness and diversity were decreased among children with severe infection. Nasopharyngeal microbiota profiles enriched in genus Dolosigranulum were related to respiratory health, while genus Haemophilus was specifically predominant in children with severe RV/EV LRTI. Children with mild or asymptomatic RV/EV infection showed an intermediate profile. Conclusions: These results suggest a close relationship between the nasopharyngeal microbiota and different clinical presentations of RV/EV infection.This project is supported by the Spanish National Health Institute Carlos III (Grant id. PI17/349). Cofunded by European Regional Development Fund/European Social Fund “A way to make Europe”/“Investing in your future.”S

Modeling the temporal dynamics of cervicovaginal microbiota identifies targets that may promote reproductive health

BACKGROUND: Cervicovaginal bacterial communities composed of diverse anaerobes with low Lactobacillus abundance are associated with poor reproductive outcomes such as preterm birth, infertility, cervicitis, and risk of sexually transmitted infections (STIs), including human immunodeficiency virus (HIV). Women in sub-Saharan Africa have a higher prevalence of these high-risk bacterial communities when compared to Western populations. However, the transition of cervicovaginal communities between high- and low-risk community states over time is not well described in African populations. RESULTS: We profiled the bacterial composition of 316 cervicovaginal swabs collected at 3-month intervals from 88 healthy young Black South African women with a median follow-up of 9 months per participant and developed a Markov-based model of transition dynamics that accurately predicted bacterial composition within a broader cross-sectional cohort. We found that Lactobacillus iners-dominant, but not Lactobacillus crispatus-dominant, communities have a high probability of transitioning to high-risk states. Simulating clinical interventions by manipulating the underlying transition probabilities, our model predicts that the population prevalence of low-risk microbial communities could most effectively be increased by manipulating the movement between L. iners- and L. crispatus-dominant communities. CONCLUSIONS: The Markov model we present here indicates that L. iners-dominant communities have a high probability of transitioning to higher-risk states. We additionally identify transitions to target to increase the prevalence of L. crispatus-dominant communities. These findings may help guide future intervention strategies targeted at reducing bacteria-associated adverse reproductive outcomes among women living in sub-Saharan Africa. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40168-021-01096-9

Modeling the temporal dynamics of cervicovaginal microbiota identifies targets that may promote reproductive health (vol 9, 163, 2021)

Following the publication of the original article [1], the authors noticed a misspelling on the name of one of the co-authors. “Musie S. Ghebermichael” should read “Musie S. Ghebremichael” The original article has been updated

Evolution of the gut microbiome following acute HIV-1 infection

Background: In rhesus macaques, simian immunodeficiency virus infection is followed by expansion of enteric viruses but has a limited impact on the gut bacteriome. To understand the longitudinal effects of HIV-1 infection on the human gut microbiota, we prospectively followed 49 Mozambican subjects diagnosed with recent HIV-1 infection (RHI) and 54 HIV-1-negative controls for 9–18 months and compared them with 98 chronically HIV-1- infected subjects treated with antiretrovirals (n = 27) or not (n = 71). Results: We show that RHI is followed by increased fecal adenovirus shedding, which persists during chronic HIV-1 infection and does not resolve with ART. Recent HIV-1 infection is also followed by transient non-HIV-specific changes in the gut bacterial richness and composition. Despite early resilience to change, an HIV-1-specific signature in the gut bacteriome—featuring depletion of Akkermansia, Anaerovibrio, Bifidobacterium, and Clostridium—previously associated with chronic inflammation, CD8+ T cell anergy, and metabolic disorders, can be eventually identified in chronically HIV-1-infected subjects. Conclusions: Recent HIV-1 infection is associated with increased fecal shedding of eukaryotic viruses, transient loss of bacterial taxonomic richness, and long-term reductions in microbial gene richness. An HIV-1-associated microbiome signature only becomes evident in chronically HIV-1-infected subjects

Mechanisms of abrupt loss of virus control in a cohort of previous HIV controllers

Altres ajuts: FIPSE grant 360737-09; AELIX TherapeuticsA few individuals can control HIV infection without the need for antiretroviral treatment and are referred to as HIV controllers. We have studied HIV controllers who suddenly lose this ability and present with high in vivo viral replication and decays in their CD4 + T-cell counts to identify potential immune and virological factors that were responsible for initial virus control. We identify in vitro -determined reductions in the ability of CD8 T cells to suppress viral control and the presence of PD-1-expressing CD8 + T cells with a naive immune phenotype as potential predictors of in vivo loss of virus control. The findings could be important for the clinical management of HIV controller individuals, and it may offer an important tool to anticipate viral rebound in individuals in clinical studies that include combination antiretroviral therapy (cART) treatment interruptions and which, if not treated quickly, could pose a significant risk to the trial participants. Elite and viremic HIV controllers are able to control their HIV infection and maintain undetectable or low-level viremia in the absence of antiretroviral treatment. Despite extensive studies, the immune factors responsible for such exclusive control remain poorly defined. We identified a cohort of 14 HIV controllers that suffered an abrupt loss of HIV control (LoC) to investigate possible mechanisms and virological and immunological events related to the sudden loss of control. The in-depth analysis of these subjects involved the study of cell tropism of circulating virus, evidence for HIV superinfection, cellular immune responses to HIV, as well as an examination of viral adaptation to host immunity by Gag sequencing. Our data demonstrate that a poor capacity of T cells to mediate in vitro viral suppression, even in the context of protective HLA alleles, predicts a loss of viral control. In addition, the data suggest that inefficient viral control may be explained by an increase of CD8 T-cell activation and exhaustion before LoC. Furthermore, we detected a switch from C5- to X4-tropic viruses in 4 individuals after loss of control, suggesting that tropism shift might also contribute to disease progression in HIV controllers. The significantly reduced inhibition of in vitro viral replication and increased expression of activation and exhaustion markers preceding the abrupt loss of viral control may help identify untreated HIV controllers that are at risk of losing control and may offer a useful tool for monitoring individuals during treatment interruption phases in therapeutic vaccine trials. IMPORTANCE A few individuals can control HIV infection without the need for antiretroviral treatment and are referred to as HIV controllers. We have studied HIV controllers who suddenly lose this ability and present with high in vivo viral replication and decays in their CD4 + T-cell counts to identify potential immune and virological factors that were responsible for initial virus control. We identify in vitro -determined reductions in the ability of CD8 T cells to suppress viral control and the presence of PD-1-expressing CD8 + T cells with a naive immune phenotype as potential predictors of in vivo loss of virus control. The findings could be important for the clinical management of HIV controller individuals, and it may offer an important tool to anticipate viral rebound in individuals in clinical studies that include combination antiretroviral therapy (cART) treatment interruptions and which, if not treated quickly, could pose a significant risk to the trial participants

Low nadir CD4+ T-cell counts predict gut dysbiosis in HIV-1 infection

Human immunodeficiency virus (HIV)-1 infection causes severe gut and systemic immune damage, but its effects on the gut microbiome remain unclear. Previous shotgun metagenomic studies in HIV-negative subjects linked low-microbial gene counts (LGC) to gut dysbiosis in diseases featuring intestinal inflammation. Using a similar approach in 156 subjects with different HIV-1 phenotypes, we found a strong, independent, dose-effect association between nadir CD4+ T-cell counts and LGC. As in other diseases involving intestinal inflammation, the gut microbiomes of subjects with LGC were enriched in gram-negative Bacteroides, acetogenic bacteria and Proteobacteria, which are able to metabolize reactive oxygen and nitrogen species; and were depleted in oxygen-sensitive methanogenic archaea and sulfate-reducing bacteria. Interestingly, subjects with LGC also showed increased butyrate levels in direct fecal measurements, consistent with enrichment in Roseburia intestinalis despite reductions in other butyrate producers. The microbiomes of subjects with LGC were also enriched in bacterial virulence factors, as well as in genes associated with beta-lactam, lincosamide, tetracycline, and macrolide resistance. Thus, low nadir CD4+ T-cell counts, rather than HIV-1 serostatus per se, predict the presence of gut dysbiosis in HIV-1 infected subjects. Such dysbiosis does not display obvious HIV-specific features; instead, it shares many similarities with other diseases featuring gut inflammation.Fundació Glòria SolerFundació Catalunya-La PedreraGala SIDA 2015-2016Nit per la Recerca a la Catalunya Central 2015 editionPeople in Red-Barcelona 2016 editionRED de SIDA RD16/0025/0041ISCIIIEuropean Regional Develpment Fund (ERDF)Agencia de Gestio d´Ajuts Universitaris i de Recerca (AGAUR)Secretaria d´Universitats i Recerca del Departament d´Economia i Coneixement de la Generalitat de CatalunyaMinisterio de Economia y Competitividad. EspañaUniversidad de Whashingto

Gut microbiome in HIV-1 infection

Una vegada el Virus de la Immunodeficiència Humana tipus 1 (en anglès HIV-1) infecta l’organisme hoste es produeix una ràpida i severa destrucció del teixit limfoide associat a tracte gastrointestinal que inclou, entre d’altres, significants pèrdues cel·lulars del sistema immunitari i epitelial de l’hoste. Seguidament es produeix un increment de la permeabilitat de la paret intestinal que permet la translocació microbiana. Així i doncs, productes i cèl·lules microbianes que normalment queden confinats i controlats dins la llum intestinal ara poden travessar l’epiteli intestinal i entrar en circulació sanguínia convertint-se en un nou focus d’activació immunitària i inflamació. Per la seva significant contribució en la patogènesis del HIV-1, gran part de la recerca en microbioma dels últims anys s’ha centrat en entendre els canvis que tenen lloc en les comunitats microbianes que habiten dins l’intestí humà després de la infecció per HIV-1 i de l’inici de tractament antiretroviral (en anglès ART). Els primers estudis transversals van descriure relacions contradictòries entre la riquesa i diversitat microbiana a l’intestí i la infecció per HIV-1 i van suggerir una substitució de Bacteroides per Prevotella com a conseqüència de l’adquisició viral. Aquests resultats però, no s’han confirmat ni en models animals ni en estudis balancejats per grups de risc de transmissió de VIH-1. En estudis en models de primats no humans la infecció pel virus de la immunodeficiància de simi s’ha associat a una expansió de les comunitats víriques intestinals però no s’ha descrit un canvi consistent en les comunitats bacterianes. En dues cohorts europees independents de persones amb infecció crònica per HIV-1 i persones no infectades de Barcelona (n=156) i Estocolm (n=84), els individus homosexuals (en anglès MSM), presentaven una microbiota intestinal més rica i diversa i una major abundància relativa de Prevotella, en comparació amb individus heterosexuals (no-MSM) que estaven enriquits per Bacteroides, independentment de la infecció per HIV-1. Estratificant els grups d’estudi en funció de la seva preferència sexual (MSM vs non-MSM), individus infectats amb HIV-1 presentaven valors inferiors de riquesa i diversitat bacteriana, amb els valorsmés baixos en el grup de individus amb una resposta discordant a ART. Tot i així no hi havia canvis evidents respecte una disbiosi específica de infecció per VIH-1. En la nostra cohort d’estudi de Barcelona, la dieta tenia un efecte limitat sobre la composició de la microbiota intestinal. Per estudiar els efectes longitudinals de la infecció per HIV-1 en la microbiota intestinal, vam fer un seguiment de 9-18 mesos a 49 persones de Moçambic diagnosticades amb infecció recent per HIV-1 i 54 persones no infectades, i les vam comparar amb dos grups de persones amb infecció crònica per HIV-1, tan si estaven amb ART (n=27) o no (n=71). En aquest estudi, seguint la infecció recent per HIV-1, es produïa una major secreció d’Adenovirus en femta, la qual persistia en infecció crònica i no desapareixia amb l’administració de ART. Paral·lelament també vam descriure canvis transitoris no específics en la riquesa i la composició bacteriana després de la infecció recent per HIV-1. Malgrat certa resiliència inicial al canvi, sí que s’evidenciava una signatura en quan a composició bacteriana en individus amb infecció crònica per HIV-1. Aquesta signatura, que incloïa pèrdua de Akkermansia, Anaerovibrio, Bifidobacterium i Clostridium, ja ha estat prèviament associada a inflamació crònica, anergia de limfòcits T CD8+ i desordres metabòlics. En conclusió: 1) La preferència sexual és un factor de confusió important que s’hauria de considerar d’ara endavant, especialment en estudis de microbioma intestinal i HIV-1; 2) La microbiota intestinal sembla ser inicialment resilient a canviar després la infecció per HIV-1 però amb el pas del temps i progressió a fase crònica sí que apareix una signatura bacteriana amb perfil pro-inflamatori; i 3) Els canvis en la microbiota intestinal no només afecten les comunitats bacterianes sinó també, com a mínim, les comunitats víriques.Soon after Human Immunodeficiency Virus type 1 (HIV-1) infection, a severe and rapid depletion of the gut-associated lymphoid tissue occurs, including significant loss of both, immune and epithelial host cells. This is followed by an increased permeability of the intestinal cell lining which facilitates microbial translocation. Microbial cells and products that are usually contained and controlled within the intestinal lumen, can now circulate in the bloodstream and become a new source for immune activation and inflammation. Because of the significant immune imbalance in the GALT after HIV-1 infection, recent microbiome research has focused on understanding the changes occurring in the microbial communities inhabiting the human gut after HIV-1 perturbation and in response to antiretroviral treatment (ART). Initial cross-sectional studies provided contradictory associations between gut microbial richness and diversity and HIV-1 infection and suggested shifts from Bacteroides to Prevotella predominance following viral infection. Nonetheless, these results have not been confirmed in animal models or in studies matched for HIV-1 transmission risk groups. For instance, in non-human primate models Simian Immunodeficiency Virus infection is followed by expansion of enteric virome but has a limited impact on the gut bacteriome. In two independent European cross-sectionals cohorts of chronically HIV-1-infected subjects and uninfected controls, in Barcelona (n=156) and Stockholm (n=84), men-who-have-sex-with-men (MSM) showed a Prevotella-enriched gut microbiota and higher microbial richness and diversity compared to non-MSM individuals who predominantly showed a Bacteroides-enriched microbiota, regardless of HIV-1 infection. After stratifying for sexual orientation (MSM vs. non-MSM), we described lower microbial richness and diversity in HIV-1 infected subjects, more so in subjects with an immune-discordant response to ART, but there was no solid evidence of an HIV-1-specific dysbiosis. In our Barcelona cohort, diet did not have a major impact on gut microbiota composition. To understand the longitudinal effects of HIV-1 infection on the human gut microbiota, we prospectively followed 49 Mozambican subjects diagnosed with recent HIV-1 infection and 54 uninfected controls for 9-18 months and compared them with 98 chronically HIV-1-infected subjects ART-treated (n=27) or not (n=71). Recent HIV-1infection was characterized by increased fecal Adenovirus shedding, which persisted during chronic HIV-1 infection and did not resolve with ART. Recent HIV-1 infection was also followed by transient non-HIV-1-specific changes in the gut bacterial richness and composition. Despite early resilience to change, an HIV-1-specific signature in the gut bacteriome could be eventually identified in chronically HIV-1-infected subjects. Such signature featured depletion of Akkermansia, Anaerovibrio, Bifidobacterium, and Clostridium, and has been previously associated with chronic inflammation, CD8+ T-cell anergy and metabolic disorders. In conclusion: 1) Sexual practice is an important confounding factor in microbiome studies that needs to be considered, especially in HIV-1-gut microbiota studies; 2) Gut microbiota is initially resilient to change right after HIV-1 acquisition but a pro-inflammatory-bacterial signature eventually appears in chronic phases of the infection, and 3) Changes on the gut microbiota do not only impact bacterial communities, but, at least, also viral communities

Gut microbiome in HIV-1 infection /

Una vegada el Virus de la Immunodeficiència Humana tipus 1 (en anglès HIV-1) infecta l'organisme hoste es produeix una ràpida i severa destrucció del teixit limfoide associat a tracte gastrointestinal que inclou, entre d'altres, significants pèrdues cel·lulars del sistema immunitari i epitelial de l'hoste. Seguidament es produeix un increment de la permeabilitat de la paret intestinal que permet la translocació microbiana. Així i doncs, productes i cèl·lules microbianes que normalment queden confinats i controlats dins la llum intestinal ara poden travessar l'epiteli intestinal i entrar en circulació sanguínia convertint-se en un nou focus d'activació immunitària i inflamació. Per la seva significant contribució en la patogènesis del HIV-1, gran part de la recerca en microbioma dels últims anys s'ha centrat en entendre els canvis que tenen lloc en les comunitats microbianes que habiten dins l'intestí humà després de la infecció per HIV-1 i de l'inici de tractament antiretroviral (en anglès ART). Els primers estudis transversals van descriure relacions contradictòries entre la riquesa i diversitat microbiana a l'intestí i la infecció per HIV-1 i van suggerir una substitució de Bacteroides per Prevotella com a conseqüència de l'adquisició viral. Aquests resultats però, no s'han confirmat ni en models animals ni en estudis balancejats per grups de risc de transmissió de VIH-1. En estudis en models de primats no humans la infecció pel virus de la immunodeficiància de simi s'ha associat a una expansió de les comunitats víriques intestinals però no s'ha descrit un canvi consistent en les comunitats bacterianes. En dues cohorts europees independents de persones amb infecció crònica per HIV-1 i persones no infectades de Barcelona (n=156) i Estocolm (n=84), els individus homosexuals (en anglès MSM), presentaven una microbiota intestinal més rica i diversa i una major abundància relativa de Prevotella, en comparació amb individus heterosexuals (no-MSM) que estaven enriquits per Bacteroides, independentment de la infecció per HIV-1. Estratificant els grups d'estudi en funció de la seva preferència sexual (MSM vs non-MSM), individus infectats amb HIV-1 presentaven valors inferiors de riquesa i diversitat bacteriana, amb els valorsmés baixos en el grup de individus amb una resposta discordant a ART. Tot i així no hi havia canvis evidents respecte una disbiosi específica de infecció per VIH-1. En la nostra cohort d'estudi de Barcelona, la dieta tenia un efecte limitat sobre la composició de la microbiota intestinal. Per estudiar els efectes longitudinals de la infecció per HIV-1 en la microbiota intestinal, vam fer un seguiment de 9-18 mesos a 49 persones de Moçambic diagnosticades amb infecció recent per HIV-1 i 54 persones no infectades, i les vam comparar amb dos grups de persones amb infecció crònica per HIV-1, tan si estaven amb ART (n=27) o no (n=71). En aquest estudi, seguint la infecció recent per HIV-1, es produïa una major secreció d'Adenovirus en femta, la qual persistia en infecció crònica i no desapareixia amb l'administració de ART. Paral·lelament també vam descriure canvis transitoris no específics en la riquesa i la composició bacteriana després de la infecció recent per HIV-1. Malgrat certa resiliència inicial al canvi, sí que s'evidenciava una signatura en quan a composició bacteriana en individus amb infecció crònica per HIV-1. Aquesta signatura, que incloïa pèrdua de Akkermansia, Anaerovibrio, Bifidobacterium i Clostridium, ja ha estat prèviament associada a inflamació crònica, anergia de limfòcits T CD8+ i desordres metabòlics. En conclusió: 1) La preferència sexual és un factor de confusió important que s'hauria de considerar d'ara endavant, especialment en estudis de microbioma intestinal i HIV-1; 2) La microbiota intestinal sembla ser inicialment resilient a canviar després la infecció per HIV-1 però amb el pas del temps i progressió a fase crònica sí que apareix una signatura bacteriana amb perfil pro-inflamatori; i 3) Els canvis en la microbiota intestinal no només afecten les comunitats bacterianes sinó també, com a mínim, les comunitats víriques.Soon after Human Immunodeficiency Virus type 1 (HIV-1) infection, a severe and rapid depletion of the gut-associated lymphoid tissue occurs, including significant loss of both, immune and epithelial host cells. This is followed by an increased permeability of the intestinal cell lining which facilitates microbial translocation. Microbial cells and products that are usually contained and controlled within the intestinal lumen, can now circulate in the bloodstream and become a new source for immune activation and inflammation. Because of the significant immune imbalance in the GALT after HIV-1 infection, recent microbiome research has focused on understanding the changes occurring in the microbial communities inhabiting the human gut after HIV-1 perturbation and in response to antiretroviral treatment (ART). Initial cross-sectional studies provided contradictory associations between gut microbial richness and diversity and HIV-1 infection and suggested shifts from Bacteroides to Prevotella predominance following viral infection. Nonetheless, these results have not been confirmed in animal models or in studies matched for HIV-1 transmission risk groups. For instance, in non-human primate models Simian Immunodeficiency Virus infection is followed by expansion of enteric virome but has a limited impact on the gut bacteriome. In two independent European cross-sectionals cohorts of chronically HIV-1-infected subjects and uninfected controls, in Barcelona (n=156) and Stockholm (n=84), men-who-have-sex-with-men (MSM) showed a Prevotella-enriched gut microbiota and higher microbial richness and diversity compared to non-MSM individuals who predominantly showed a Bacteroides-enriched microbiota, regardless of HIV-1 infection. After stratifying for sexual orientation (MSM vs. non-MSM), we described lower microbial richness and diversity in HIV-1 infected subjects, more so in subjects with an immune-discordant response to ART, but there was no solid evidence of an HIV-1-specific dysbiosis. In our Barcelona cohort, diet did not have a major impact on gut microbiota composition. To understand the longitudinal effects of HIV-1 infection on the human gut microbiota, we prospectively followed 49 Mozambican subjects diagnosed with recent HIV-1 infection and 54 uninfected controls for 9-18 months and compared them with 98 chronically HIV-1-infected subjects ART-treated (n=27) or not (n=71). Recent HIV-1infection was characterized by increased fecal Adenovirus shedding, which persisted during chronic HIV-1 infection and did not resolve with ART. Recent HIV-1 infection was also followed by transient non-HIV-1-specific changes in the gut bacterial richness and composition. Despite early resilience to change, an HIV-1-specific signature in the gut bacteriome could be eventually identified in chronically HIV-1-infected subjects. Such signature featured depletion of Akkermansia, Anaerovibrio, Bifidobacterium, and Clostridium, and has been previously associated with chronic inflammation, CD8+ T-cell anergy and metabolic disorders. In conclusion: 1) Sexual practice is an important confounding factor in microbiome studies that needs to be considered, especially in HIV-1-gut microbiota studies; 2) Gut microbiota is initially resilient to change right after HIV-1 acquisition but a pro-inflammatory-bacterial signature eventually appears in chronic phases of the infection, and 3) Changes on the gut microbiota do not only impact bacterial communities, but, at least, also viral communities