SARS-CoV-2 humoral immunity in people living with HIV-1 Motsoeneng, Boitumelo M.; Bhiman, Jinal N.; Richardson, Simone I. ...
Trends in immunology,
July 2024, 2024-07-00, 20240701, Letnik:
45, Številka:
7
Journal Article
Recenzirano
Odprti dostop
People living with HIV-1 (PLWH) on antiretroviral treatment (ART) present with delayed infection- and vaccine-induced humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ...compared with people without HIV-1 (PWOH). However, they eventually reach titers equivalent to those of PWOH.Differential coordination of SARS-CoV-2 Fc effector functions suggests that antibody responses are qualitatively variable in PLWH, with potential implications for vaccination.Intrahost diversity is more pronounced in ART-naive PLWH, who may contribute to the divergence of SARS-CoV-2 lineages and/or the emergence of variants of concern.Existing data on SARS-CoV-2 humoral immunity and intrahost diversity in PLWH supports the need to increase access to ART.
Given the substantial number of people living with HIV-1 (PLWH), especially in sub-Saharan Africa, understanding the effectiveness of COVID-19 vaccines and antibody responses to SARS-CoV-2 infection and vaccination is essential. Additionally, the impact of pre-existing immunity against endemic human coronaviruses on SARS-CoV-2 responses in PLWH remains underexplored. Prolonged SARS-CoV-2 shedding, and enhanced intrahost diversity observed for PLWH, might be one of the driving forces behind SARS-CoV-2 evolution in Africa and should be further considered, with public health implications worldwide.
The effect of COVID-19 on the high number of immunocompromised people living with HIV-1 (PLWH), particularly in Africa, remains a critical concern. Here, we identify key areas that still require further investigation, by examining COVID-19 vaccine effectiveness, and understanding antibody responses in SARS-CoV-2 infection and vaccination in comparison with people without HIV-1 (PWOH). We also assess the potential impact of pre-existing immunity against endemic human coronaviruses on SARS-CoV-2 responses in these individuals. Lastly, we discuss the consequences of persistent infection in PLWH (or other immunocompromised individuals), including prolonged shedding, increased viral diversity within the host, and the implications on SARS-CoV-2 evolution in Africa.
The effect of COVID-19 on the high number of immunocompromised people living with HIV-1 (PLWH), particularly in Africa, remains a critical concern. Here, we identify key areas that still require further investigation, by examining COVID-19 vaccine effectiveness, and understanding antibody responses in SARS-CoV-2 infection and vaccination in comparison with people without HIV-1 (PWOH). We also assess the potential impact of pre-existing immunity against endemic human coronaviruses on SARS-CoV-2 responses in these individuals. Lastly, we discuss the consequences of persistent infection in PLWH (or other immunocompromised individuals), including prolonged shedding, increased viral diversity within the host, and the implications on SARS-CoV-2 evolution in Africa.
Abstract
The phylum Nucleocytoviricota includes the largest and most complex viruses known. These “giant viruses” have a long evolutionary history that dates back to the early diversification of ...eukaryotes, and over time they have evolved elaborate strategies for manipulating the physiology of their hosts during infection. One of the most captivating of these mechanisms involves the use of genes acquired from the host—referred to here as viral homologs or “virologs”—as a means of promoting viral propagation. The best-known examples of these are involved in mimicry, in which viral machinery “imitates” immunomodulatory elements in the vertebrate defense system. But recent findings have highlighted a vast and rapidly expanding array of other virologs that include many genes not typically found in viruses, such as those involved in translation, central carbon metabolism, cytoskeletal structure, nutrient transport, vesicular trafficking, and light harvesting. Unraveling the roles of virologs during infection as well as the evolutionary pathways through which complex functional repertoires are acquired by viruses are important frontiers at the forefront of giant virus research.
The authors discuss recent research into the complex functions encoded in the genomes of giant viruses.
Spindle- or lemon-shaped viruses infect archaea in diverse environments. Due to the highly pleomorphic nature of these virions, which can be found with cylindrical tails emanating from the ...spindle-shaped body, structural studies of these capsids have been challenging. We have determined the atomic structure of the capsid of Sulfolobus monocaudavirus 1, a virus that infects hosts living in nearly boiling acid. A highly hydrophobic protein, likely integrated into the host membrane before the virions assemble, forms 7 strands that slide past each other in both the tails and the spindle body. We observe the discrete steps that occur as the tail tubes expand, and these are due to highly conserved quasiequivalent interactions with neighboring subunits maintained despite significant diameter changes. Our results show how helical assemblies can vary their diameters, becoming nearly spherical to package a larger genome and suggest how all spindle-shaped viruses have evolved from archaeal rod-like viruses.
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•We present the first atomic structure of an archaeal spindle-shaped virus•Spindle-shaped viruses have evolved from archaeal rod-shaped viruses•Hydrophobic interactions underlie the pleomorphism of spindle-shaped capsids
Structural analysis of an archaea-specific virus reveals principles for how filamentous assemblies of hydrophobic proteins can readily accommodate changes in morphology relevant for virus evolution and potentially for contexts as diverse as eukaryotic membrane dynamics and intermediate filaments.
Since the end of 2019, the world has been challenged by the coronavirus disease 2019 (COVID-19) pandemic. With COVID-19 cases rising globally, severe acute respiratory syndrome coronavirus 2 ...(SARS-CoV-2) continues to evolve, resulting in the emergence of variants of interest (VOI) and of concern (VOC). Of the hundreds of millions infected, immunodeficient patients are one of the vulnerable cohorts that are most susceptible to this virus. These individuals include those with preexisting health conditions and/or those undergoing immunosuppressive treatment (secondary immunodeficiency). In these cases, several researchers have reported chronic infections in the presence of anti-COVID-19 treatments that may potentially lead to the evolution of the virus within the host. Such variations occurred in a variety of viral proteins, including key structural ones involved in pathogenesis such as spike proteins. Tracking and comparing such mutations with those arisen in the general population may provide information about functional sites within the SARS-CoV-2 genome. In this study, we reviewed the current literature regarding the specific features of SARS-CoV-2 evolution in immunocompromised patients and identified recurrent
de novo
amino acid changes in virus isolates of these patients that can potentially play an important role in SARS-CoV-2 pathogenesis and evolution.
To control viral infection, vertebrates rely on both inducible interferon responses and less well-characterized cell-intrinsic responses composed of “at the ready” antiviral effector proteins. Here, ...we show that E3 ubiquitin ligase TRIM7 is a cell-intrinsic antiviral effector that restricts multiple human enteroviruses by targeting viral 2BC, a membrane remodeling protein, for ubiquitination and proteasome-dependent degradation. Selective pressure exerted by TRIM7 results in emergence of a TRIM7-resistant coxsackievirus with a single point mutation in the viral 2C ATPase/helicase. In cultured cells, the mutation helps the virus evade TRIM7 but impairs optimal viral replication, and this correlates with a hyperactive and structurally plastic 2C ATPase. Unexpectedly, the TRIM7-resistant virus has a replication advantage in mice and causes lethal pancreatitis. These findings reveal a unique mechanism for targeting enterovirus replication and provide molecular insight into the benefits and trade-offs of viral evolution imposed by a host restriction factor.
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•cDNA screen reveals E3 ligase TRIM7 as a potent inhibitor of human enteroviruses•TRIM7 targets viral 2BC protein for ubiquitination and degradation•A single T323A amino acid change in viral 2C protein confers resistance to TRIM7•TRIM7-resistant viral variant replicates robustly in mice and causes severe disease
The E3 ubiquitin ligase TRIM7 is an antiviral effector that restricts multiple human enteroviruses.
The rapid spread and remarkable mutations of SARS‐CoV‐2 variants, particularly Omicron, necessitate an understanding of their evolutionary characteristics. In this study, we analyzed representative ...high‐quality whole‐genome sequences of 2008 SARS‐CoV‐2 variants to explore long‐term dynamic changes in genomic base (especially GC) content and variations during viral evolution. Our results demonstrated a highly negative correlation between GC content and variant emergence time (r = −0.765, p < 2.22e−16). Major gene partitions (S, N, ORF1ab) displayed similar trends. Omicron exhibited a significantly lower GC content than non‐Omicron variants (p < 2.22e−16). Notably, we observed a robust negative correlation between C and T content (r = −0.778, p < 2.22e−16) and between G and A content (r = −0.773, p < 2.22e−16). Among all strains, Omicron showed the greatest base variation, with C‐>T mutations being the most frequent (median interquartile range IQR: 29 (27, 31), 37.67%), succeeded by G‐>A mutations (11 (9, 13), 14.63%). Over a 3‐year span, an annual decline rate of 0.12% in SARS‐CoV‐2 GC content was observed and could become more pronounced in future emerging variants. These findings provided insights into the evolutionary trajectory of SARS‐CoV‐2, underscoring the significance of continuous genomic surveillance for effective prediction of and response to future variants.
Because of HIV's vast sequence diversity, the ability of the CD8 T-cell response to recognize several variants of a single epitope is an important consideration for vaccine design. Cross-recognition ...of viral epitopes by CD8 T cells is associated with viral control during HIV-1 infection, but little is known about CD8 cross-reactivity in the context of HIV-1 vaccination. Here, we evaluated vaccine-induced CD8 cross-reactivity in two preventative HIV-1 vaccine efficacy trials, the MRKAd5 and DNA/rAd5 studies. Cross-reactive CD8 responses elicited by vaccination were similar in magnitude and frequency to those induced during acute HIV-1 infection. Although responses directed against variant epitopes were less avid than responses to vaccine-matched epitopes, we did not detect any difference in response polyfunctionality (the proportion of cells producing multiple effector molecules). And while depth, or the frequency of cross-reactive responses, did not correlate with viral loads in recipients who became infected, cross-reactivity did appear to influence early viral evolution. In comparing viral sequences of placebo versus vaccine recipients, we found that viral sequences from vaccinees encoded CD8 epitopes with more substitutions and greater biochemical dissimilarity. In other words, breakthrough sequences of vaccinees would be less cross-recognized by vaccine-induced responses. Additionally, vaccine-induced CD8 T cells poorly cross-recognized variant epitopes encoding HLA-I-associated adaptations, further supporting our conclusion that these responses play a role in driving early HIV-1 viral evolution.
HIV-1 has exceptionally high sequence diversity, much of which is found within CD8 epitopes. Therefore, the ability of CD8 T cells to recognize multiple versions of a single epitope could be important for an effective vaccine. Here, we show that two previously tested vaccines induced a similar level of CD8 cross-reactivity to that seen in acute HIV-1 infection. Although this cross-reactivity did not seem to affect viral control in vaccine recipients who became infected, we identified several ways in which CD8 cross-reactivity appeared to influence HIV-1 viral evolution. First, we saw that strains isolated from infected vaccine recipients would likely be poorly cross-recognized by the vaccine-induced response. Second, we saw that adapted CD8 epitopes were poorly cross-recognized in both vaccination and infection. Collectively, we believe these results show that CD8 cross-reactivity could be an important consideration in future HIV-1 vaccine design.
Rodents represent around 43% of all mammalian species, are widely distributed, and are the natural reservoirs of a diverse group of zoonotic viruses, including hantaviruses, Lassa viruses, and ...tick-borne encephalitis viruses. Thus, analyzing the viral diversity harbored by rodents could assist efforts to predict and reduce the risk of future emergence of zoonotic viral diseases.
We used next-generation sequencing metagenomic analysis to survey for a range of mammalian viral families in rodents and other small animals of the orders Rodentia, Lagomorpha, and Soricomorpha in China. We sampled 3,055 small animals from 20 provinces and then outlined the spectra of mammalian viruses within these individuals and the basic ecological and genetic characteristics of novel rodent and shrew viruses among the viral spectra. Further analysis revealed that host taxonomy plays a primary role and geographical location plays a secondary role in determining viral diversity. Many viruses were reported for the first time with distinct evolutionary lineages, and viruses related to known human or animal pathogens were identified. Phylogram comparison between viruses and hosts indicated that host shifts commonly happened in many different species during viral evolutionary history.
These results expand our understanding of the viromes of rodents and insectivores in China and suggest that there is high diversity of viruses awaiting discovery in these species in Asia. These findings, combined with our previous bat virome data, greatly increase our knowledge of the viral community in wildlife in a densely populated country in an emerging disease hotspot.
Circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the human population leads to further viral evolution. The new variants that arise during this evolution are more ...infectious. Our data suggest that newer variants have shifted from utilizing both cathepsin/endosome- and TMPRSS2-mediated entry mechanisms to rely on a TMPRSS2-dependent entry pathway. Accordingly, only the early lineages of SARS-CoV-2 are capable of infecting and forming syncytia in Vero/ACE2 cells which lack TMPRSS2 expression. The presence of an intact multibasic furin cleavage site (FCS) in the S protein was a key requirement for cell-to-cell fusion. Deletion of FCS makes SARS-CoV-2 more infectious in vitro but renders it incapable of syncytium formation. Cell-to-cell fusion likely represents an alternative means of virus spread and is resistant to the presence of high levels of neutralizing monoclonal antibodies (MAbs) and immune sera in the media. In this study, we also noted that cells infected with SARS-CoV-2 with an intact FCS or alphavirus replicon expressing S protein (VEErep/S) released high levels of free S1 subunit. The released S1 is capable of activating the TLR4 receptor and inducing a pro-inflammatory response. Thus, S1 activation of TLR4 may be an important contributor to SARS-CoV-2-induced COVID-19 disease and needs to be considered in the design of COVID mRNA vaccines. Lastly, a VEErep/S-replicon was shown to produce large amounts of infectious, syncytium-forming pseudoviruses and thus could represent alternative experimental system for screening inhibitors of virus entry and syncytium formation. IMPORTANCE The results of this study demonstrate that the late lineages of SARS-CoV-2 evolved to more efficient use of the TMPRSS2-mediated entry pathway and gradually lost an ability to employ the cathepsins/endosome-mediated entry. The acquisition of a furin cleavage site (FCS) by SARS-CoV-2-specific S protein made the virus a potent producer of syncytia. Their formation is also determined by expression of ACE2 and TMPRSS2 and is resistant to neutralizing human MAbs and immune sera. Syncytium formation appears to be an alternative means of infection spread following the development of an adaptive immune response. Cells infected with SARS-CoV-2 with an intact FCS secrete high levels of the S1 subunit. The released S1 demonstrates an ability to activate the TLR4 receptor and induce pro-inflammatory cytokines, which represent a hallmark of SARS-CoV-2 pathogenesis. Alphavirus replicons encoding SARS-CoV-2 S protein cause spreading, syncytium-forming infection, and they can be applied as an experimental tool for studying the mechanism of syncytium formation.
Sequencing of viral infections has become increasingly common over the last decade. Deep sequencing data in particular have proven useful in characterizing the roles that genetic drift and natural ...selection play in shaping within-host viral populations. They have also been used to estimate transmission bottleneck sizes from identified donor-recipient pairs. These bottleneck sizes quantify the number of viral particles that establish genetic lineages in the recipient host and are important to estimate due to their impact on viral evolution. Current approaches for estimating bottleneck sizes exclusively consider the subset of viral sites that are observed as polymorphic in the donor individual. However, these approaches have the potential to substantially underestimate true transmission bottleneck sizes. Here, we present a new statistical approach for instead estimating bottleneck sizes using patterns of viral genetic variation that arise de novo within a recipient individual. Specifically, our approach makes use of the number of clonal viral variants observed in a transmission pair, defined as the number of viral sites that are monomorphic in both the donor and the recipient but carry different alleles. We first test our approach on a simulated dataset and then apply it to both influenza A virus sequence data and SARS-CoV-2 sequence data from identified transmission pairs. Our results confirm the existence of extremely tight transmission bottlenecks for these 2 respiratory viruses.
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