Multiple factors over the lifetime of an individual, including diet, geography, and physiologic state, will influence the microbial communities within the primate gut. To determine the source of ...variation in the composition of the microbiota within and among species, we investigated the distal gut microbial communities harbored by great apes, as present in fecal samples recovered within their native ranges. We found that the branching order of host-species phylogenies based on the composition of these microbial communities is completely congruent with the known relationships of the hosts. Although the gut is initially and continuously seeded by bacteria that are acquired from external sources, we establish that over evolutionary timescales, the composition of the gut microbiota among great ape species is phylogenetically conserved and has diverged in a manner consistent with vertical inheritance.
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The barrier to curing HIV-1 is thought to reside primarily in CD4+ T cells containing silent proviruses. To characterize these latently infected cells, we studied the integration profile of HIV-1 in ...viremic progressors, individuals receiving antiretroviral therapy, and viremic controllers. Clonally expanded T cells represented the majority of all integrations and increased during therapy. However, none of the 75 expanded T cell clones assayed contained intact virus. In contrast, the cells bearing single integration events decreased in frequency over time on therapy, and the surviving cells were enriched for HIV-1 integration in silent regions of the genome. Finally, there was a strong preference for integration into, or in close proximity to, Alu repeats, which were also enriched in local hotspots for integration. The data indicate that dividing clonally expanded T cells contain defective proviruses and that the replication-competent reservoir is primarily found in CD4+ T cells that remain relatively quiescent.
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•Integration sequencing identifies clonally expanded and single HIV-1 integrations in human subjects•Large clonal families of HIV-1+ cells are likely not part of the latent reservoir•HIV-1 integrates near or into a 30 bp INT-motif found in Alu repeats
HIV-1-infected CD4+ T cells that undergo clonal expansion are able to proliferate because their proviruses are defective. Conversely, the replication-competent reservoir is likely found in the subset of CD4+ T cells that carry unique integrations and remain quiescent.
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Development of an effective AIDS vaccine is a global priority. However, the extreme diversity of HIV type 1 (HIV-1), which is a consequence of its propensity to mutate to escape immune responses, ...along with host factors that prevent the elicitation of protective immune responses, continue to hinder vaccine development. Breakthroughs in understanding of the biology of the transmitted virus, the structure and nature of its envelope trimer, vaccine-induced CD8 T cell control in primates, and host control of broadly neutralizing antibody elicitation have given rise to new vaccine strategies. Despite this promise, emerging data from preclinical trials reinforce the need for additional insight into virus—host biology in order to facilitate the development of a successful vaccine.
New breakthroughs have expanded our understanding of HIV, including the transmitted virus, envelope trimer structure, vaccine-induced T cells, and neutralizing antibodies. Haynes et al. examine how these advances have led to HIV vaccine strategies and discuss the need for additional insight into virus—host biology to facilitate successful vaccine development.
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Ape Origins of Human Malaria Sharp, Paul M; Plenderleith, Lindsey J; Hahn, Beatrice H
Annual review of microbiology,
09/2020, Volume:
74, Issue:
1
Journal Article
Peer reviewed
Open access
African apes harbor at least twelve
Plasmodium
species, some of which have been a source of human infection. It is now well established that
Plasmodium falciparum
emerged following the transmission ...of a gorilla parasite, perhaps within the last 10,000 years, while
Plasmodium vivax
emerged earlier from a parasite lineage that infected humans and apes in Africa before the Duffy-negative mutation eliminated the parasite from humans there. Compared to their ape relatives, both human parasites have greatly reduced genetic diversity and an excess of nonsynonymous mutations, consistent with severe genetic bottlenecks followed by rapid population expansion. A putative new
Plasmodium
species widespread in chimpanzees, gorillas, and bonobos places the origin of
Plasmodium malariae
in Africa. Here, we review what is known about the origins and evolutionary history of all human-infective
Plasmodium
species, the time and circumstances of their emergence, and the diversity, host specificity, and zoonotic potential of their ape counterparts.
Interferon-induced transmembrane proteins (IFITMs) restrict the entry of diverse enveloped viruses through incompletely understood mechanisms. While IFITMs are reported to inhibit HIV-1, their ...in vivo relevance is unclear. We show that IFITM sensitivity of HIV-1 strains is determined by the co-receptor usage of the viral envelope glycoproteins as well as IFITM subcellular localization within the target cell. Importantly, we find that transmitted founder HIV-1, which establishes de novo infections, is uniquely resistant to the antiviral activity of IFITMs. However, viral sensitivity to IFITMs, particularly IFITM2 and IFITM3, increases over the first 6 months of infection, primarily as a result of neutralizing antibody escape mutations. Additionally, the ability to evade IFITM restriction contributes to the different interferon sensitivities of transmitted founder and chronic viruses. Together, these data indicate that IFITMs constitute an important barrier to HIV-1 transmission and that escape from adaptive immune responses exposes the virus to antiviral restriction.
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•IFITM restriction of HIV-1 depends on virus co-receptor use and IFITM localization•Transmitted founder viruses are resistant to IFITM restriction•Escape from early neutralizing antibodies confers IFITM sensitivity•IFITM restriction contributes to the increased IFN sensitivity of chronic viruses
IFITMs are interferon-induced proteins with broad antiviral activity. Foster et al. demonstrate that HIV-1 sensitivity to IFITMs depends on the viral entry route into target cells. Strikingly, transmitted HIV-1 strains are IFITM resistant, but viral envelope mutations that escape neutralizing antibody responses after infection lead to IFITM and interferon sensitivity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The evolution of HIV-1 and the origin of AIDS Sharp, Paul M.; Hahn, Beatrice H.
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
08/2010, Volume:
365, Issue:
1552
Journal Article
Peer reviewed
Open access
The major cause of acquired immune deficiency syndrome (AIDS) is human immunodeficiency virus type 1 (HIV-1). We have been using evolutionary comparisons to trace (i) the origin(s) of HIV-1 and (ii) ...the origin(s) of AIDS. The closest relatives of HIV-1 are simian immunodeficiency viruses (SIVs) infecting wild-living chimpanzees (Pan troglodytes troglodytes) and gorillas (Gorilla gorilla gorilla) in west central Africa. Phylogenetic analyses have revealed the origins of HIV-1: chimpanzees were the original hosts of this clade of viruses; four lineages of HIV-1 have arisen by independent cross-species transmissions to humans and one or two of those transmissions may have been via gorillas. However, SIVs are primarily monkey viruses: more than 40 species of African monkeys are infected with their own, species-specific, SIV and in at least some host species, the infection seems non-pathogenic. Chimpanzees acquired from monkeys two distinct forms of SIVs that recombined to produce a virus with a unique genome structure. We have found that SIV infection causes CD4+ T-cell depletion and increases mortality in wild chimpanzees, and so the origin of AIDS is more ancient than the origin of HIV-1. Tracing the genetic changes that occurred as monkey viruses adapted to infect first chimpanzees and then humans may provide insights into the causes of the pathogenicity of these viruses.
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Significance Human lifestyles profoundly influence the communities of microorganisms that inhabit the body, that is, the microbiome; however, how the microbiomes of humans have diverged from those ...found within wild-living hominids is not clear. To establish how the gut microbiome has changed since the diversification of human and ape species, we characterized the microbial assemblages residing within hundreds of wild chimpanzees, bonobos, and gorillas. Changes in the composition of the microbiome accrued steadily as African apes diversified, but human microbiomes have diverged at an accelerated pace owing to a dramatic loss of ancestral microbial diversity. These results suggest that the human microbiome has undergone a substantial transformation since the human–chimpanzee split.
Humans are ecosystems containing trillions of microorganisms, but the evolutionary history of this microbiome is obscured by a lack of knowledge about microbiomes of African apes. We sequenced the gut communities of hundreds of chimpanzees, bonobos, and gorillas and developed a phylogenetic approach to reconstruct how present-day human microbiomes have diverged from those of ancestral populations. Compositional change in the microbiome was slow and clock-like during African ape diversification, but human microbiomes have deviated from the ancestral state at an accelerated rate. Relative to the microbiomes of wild apes, human microbiomes have lost ancestral microbial diversity while becoming specialized for animal-based diets. Individual wild apes cultivate more phyla, classes, orders, families, genera, and species of bacteria than do individual humans across a range of societies. These results indicate that humanity has experienced a depletion of the gut flora since diverging from Pan .
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Acquired immunodeficiency syndrome (AIDS) of humans is caused by two lentiviruses, human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2). Here, we describe the origins and evolution of these ...viruses, and the circumstances that led to the AIDS pandemic. Both HIVs are the result of multiple cross-species transmissions of simian immunodeficiency viruses (SIVs) naturally infecting African primates. Most of these transfers resulted in viruses that spread in humans to only a limited extent. However, one transmission event, involving SIVcpz from chimpanzees in southeastern Cameroon, gave rise to HIV-1 group M-the principal cause of the AIDS pandemic. We discuss how host restriction factors have shaped the emergence of new SIV zoonoses by imposing adaptive hurdles to cross-species transmission and/or secondary spread. We also show that AIDS has likely afflicted chimpanzees long before the emergence of HIV. Tracing the genetic changes that occurred as SIVs crossed from monkeys to apes and from apes to humans provides a new framework to examine the requirements of successful host switches and to gauge future zoonotic risk.
T-cell immunity is likely to play a role in protection against SARS-CoV-2 by helping generate neutralizing antibodies. We longitudinally studied CD4 T-cell responses to the M, N, and S structural ...proteins of SARS-CoV-2 in 26 convalescent individuals. Within the first two months following symptom onset, a majority of individuals (81%) mounted at least one CD4 T-cell response, and 48% of individuals mounted detectable SARS-CoV-2-specific circulating T follicular helper cells (cTfh, defined as CXCR5
+
PD1
+
CD4 T cells). SARS-CoV-2-specific cTfh responses across all three protein specificities correlated with antibody neutralization with the strongest correlation observed for S protein-specific responses. When examined over time, cTfh responses, particularly to the M protein, increased in convalescence, and robust cTfh responses with magnitudes greater than 5% were detected at the second convalescent visit, a median of 38 days post-symptom onset. CD4 T-cell responses declined but persisted at low magnitudes three months and six months after symptom onset. These data deepen our understanding of antigen-specific cTfh responses in SARS-CoV-2 infection, suggesting that in addition to S protein, M and N protein-specific cTfh may also assist in the development of neutralizing antibodies and that cTfh response formation may be delayed in SARS-CoV-2 infection.
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•Chimpanzees and gorillas harbour six Laverania spp. as well as Plasmodium vivax.•Plasmodium falciparum arose in humans after the acquisition of the parasite from a ...gorilla.•Plasmodium vivax is a bottlenecked parasite lineage that originated in African apes.
Plasmodium falciparum and Plasmodium vivax account for more than 95% of all human malaria infections, and thus pose a serious public health challenge. To control and potentially eliminate these pathogens, it is important to understand their origins and evolutionary history. Until recently, it was widely believed that P. falciparum had co-evolved with humans (and our ancestors) over millions of years, whilst P. vivax was assumed to have emerged in southeastern Asia following the cross-species transmission of a parasite from a macaque. However, the discovery of a multitude of Plasmodium spp. in chimpanzees and gorillas has refuted these theories and instead revealed that both P. falciparum and P. vivax evolved from parasites infecting wild-living African apes. It is now clear that P. falciparum resulted from a recent cross-species transmission of a parasite from a gorilla, whilst P. vivax emerged from an ancestral stock of parasites that infected chimpanzees, gorillas and humans in Africa, until the spread of the protective Duffy-negative mutation eliminated P. vivax from human populations there. Although many questions remain concerning the biology and zoonotic potential of the P. falciparum- and P. vivax-like parasites infecting apes, comparative genomics, coupled with functional parasite and vector studies, are likely to yield new insights into ape Plasmodium transmission and pathogenesis that are relevant to the treatment and prevention of human malaria.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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