Viral Hosts Research Articles

The role of pipe biofilms on dissemination of viral pathogens and virulence factor genes in a full-scale drinking water supply system

Water is an important medium for virus transmission and viral pathogens are increasingly appreciated as a significant water safety issue. However, the effect of pipe biofilms on viral pathogens remains unclear. This research aimed to investigate the dissemination of viruses in a full-scale drinking water supply system (DWSS) and the effect of pipe biofilms on viral pathogens in bulking water. Viral pathogens, pathogenic viral hosts, and viral virulence factors (VFs) were found to disseminate from source water to tap water. The proportion of virus and viral VFs in the biofilm was far less than that in water. The contribution of biofilms in pipe wall to viruses and viral VFs in bulking water was less than 4%, and viruses in the biofilm had no obvious effect on pathogenic viruses in water. Dominant viruses carrying VFs changed from Cyanobacteria virus to Mycobacterium virus after advanced water treatment. Mycobacterium and organics were identified as the key factors influencing composition and abundance of viral VFs, which could explain 41.1% of the variation in viral virulence in the water supply system. Host bacteria and organics may be used as the key targets to control the risk of viruses in DWSSs.

A phage parasite deploys a nicking nuclease effector to inhibit viral host replication.

PLEs (phage-inducible chromosomal island-like elements) are phage parasites integrated into the chromosome of epidemic Vibrio cholerae. In response to infection by its viral host ICP1, PLE excises, replicates and hijacks ICP1 structural components for transduction. Through an unknown mechanism, PLE prevents ICP1 from transitioning to rolling circle replication (RCR), a prerequisite for efficient packaging of the viral genome. Here, we characterize a PLE-encoded nuclease, NixI, that blocks phage development likely by nicking ICP1’s genome as it transitions to RCR. NixI-dependent cleavage sites appear in ICP1’s genome during infection of PLE(+) V. cholerae. Purified NixI demonstrates in vitro nuclease activity specifically for sites in ICP1’s genome and we identify a motif that is necessary for NixI-mediated cleavage. Importantly, NixI is sufficient to limit ICP1 genome replication and eliminate progeny production, representing the most inhibitory PLE-encoded mechanism revealed to date. We identify distant NixI homologs in an expanded family of putative phage parasites in vibrios that lack nucleotide homology to PLEs but nonetheless share genomic synteny with PLEs. More generally, our results reveal a previously unknown mechanism deployed by phage parasites to limit packaging of their viral hosts’ genome and highlight the prominent role of nuclease effectors as weapons in the arms race between antagonizing genomes.

Severity of Viral Diseases and Types of Weeds as Alternative Viral Hosts in <em>Dioscorea</em> Fields in Southern Guinea Savannah Agroecology of Nigeria

Journal of Food and Agriculture is a half yearly publication by the Faculty of Agriculture and Plantation Management and Faculty of Livestock fisheries and Nutrition of the Wayamba University of Sri Lanka which provides a valuable forum for scientists endeavoring in research and development aspects in agriculture, food and nutrition. Full text articles available.

Virus diversity in metagenomes of a lichen symbiosis (Umbilicaria phaea): complete viral genomes, putative hosts and elevational distributions.

Viruses can play critical roles in symbioses by initiating horizontal gene transfer, affecting host phenotypes, or expanding their host's ecological niche. However, knowledge of viral diversity and distribution in symbiotic organisms remains elusive. Here we use deep-sequenced metagenomic DNA (PacBio Sequel II; two individuals), paired with a population genomics approach (Pool-seq; 11 populations, 550 individuals) to understand viral distributions in the lichen Umbilicaria phaea. We assess (i) viral diversity in lichen thalli, (ii) putative viral hosts (fungi, algae, bacteria) and (iii) viral distributions along two replicated elevation gradients. We identified five novel viruses, showing 28%-40% amino acid identity to known viruses. They tentatively belong to the families Caulimoviridae, Myoviridae, Podoviridae and Siphoviridae. Our analysis suggests that the Caulimovirus is associated with green algal photobionts (Trebouxia) of the lichen, and the remaining viruses with bacterial hosts. We did not detect viral sequences in the mycobiont. Caulimovirus abundance decreased with increasing elevation, a pattern reflected by a specific algal lineage hosting this virus. Bacteriophages showed population-specific patterns. Our work provides the first comprehensive insights into viruses associated with a lichen holobiont and suggests an interplay of viral hosts and environment in structuring viral distributions.

VirusMED: an atlas of hotspots of viral proteins.

Metal binding sites, antigen epitopes and drug binding sites are the hotspots in viral proteins that control how viruses interact with their hosts. virusMED (virus Metal binding sites, Epitopes and Drug binding sites) is a rich internet application based on a database of atomic interactions around hotspots in 7041 experimentally determined viral protein structures. 25306 hotspots from 805 virus strains from 75 virus families were characterized, including influenza, HIV-1 and SARS-CoV-2 viruses. Just as Google Maps organizes and annotates points of interest, virusMED presents the positions of individual hotspots on each viral protein and creates an atlas upon which newly characterized functional sites can be placed as they are being discovered. virusMED contains an extensive set of annotation tags about the virus species and strains, viral hosts, viral proteins, metal ions, specific antibodies and FDA-approved drugs, which permits rapid screening of hotspots on viral proteins tailored to a particular research problem. The virusMED portal (https://virusmed.biocloud.top) can serve as a window to a valuable resource for many areas of virus research and play a critical role in the rational design of new preventative and therapeutic agents targeting viral infections.

Wild meat trade over the last 45 years in the Peruvian Amazon.

The trade in wild meat is an important economic component of rural people's livelihoods, but it has been perceived to be among the main causes of the decline of wildlife species. Recently, the COVID-19 pandemic has brought to light an additional concern of wildlife markets as a major human-health challenge. We analyzed data from the largest longitudinal monitoring (1973-2018) of the most important urban wild-meat markets in Iquitos, Peru, to examine the trends in and impacts of these markets on people's livelihoods. Over the last 45 years, wild meat sales increased at a rate of 6.4 t/year (SD 2.17), paralleling urban population growth. Wild meat sales were highest in 2018 (442 t), contributing US$2.6 million (0.76%) to the regional gross domestic product. Five species of ungulates and rodents accounted for 88.5% of the amount of biomass traded. Vulnerable and Endangered species represented 7.0% and 0.4% of individuals sold, respectively. Despite growth in sales, the contribution of wild meat to overall urban diet was constant: 1-2%/year of total meat consumed. This result was due to greater availability and higher consumption of cheaper meats (e.g., in 2018, poultry was 45.8% cheaper and was the most consumed meat) coupled with the lack of economic incentives to harvest wild meat species in rural areas. Most wild meat was sold salted or smoked, reducing the likelihood of foodborne diseases. Community-based wildlife management plans and the continued trade bans on primates and threatened taxa may avoid biodiversity loss. Considering the recent COVID-19 pandemic, future management plans should include potential viral hosts and regulation and enforcement of hygiene practices in wild-meat markets.

Ecogenomics of Groundwater Phages Suggests Niche Differentiation Linked to Specific Environmental Tolerance.

ABSTRACTViruses are ubiquitous microbiome components, shaping ecosystems via strain-specific predation, horizontal gene transfer and redistribution of nutrients through host lysis. Viral impacts are important in groundwater ecosystems, where microbes drive many nutrient fluxes and metabolic processes; however, little is known about the diversity of viruses in these environments. We analyzed four groundwater plasmidomes (the entire plasmid content of an environment) and identified 200 viral sequences, which clustered into 41 genus-level viral clusters (approximately equivalent to viral genera) including 9 known and 32 putative new genera. We used publicly available bacterial whole-genome sequences (WGS) and WGS from 261 bacterial isolates from this groundwater environment to identify potential viral hosts. We linked 76 of the 200 viral sequences to a range of bacterial phyla, the majority associated with Proteobacteria, followed by Firmicutes, Bacteroidetes, and Actinobacteria. The publicly available WGS enabled mapping bacterial hosts to several viral sequences. The WGS of groundwater isolates increased the depth of host prediction by allowing host identification at the strain level. The latter included 4 viruses that were almost entirely (>99% query coverage, >99% identity) identified as integrated in the genomes of Pseudomonas, Acidovorax, and Castellaniella strains, resulting in high-confidence host assignments. Lastly, 21 of these viruses carried putative auxiliary metabolite genes for metal and antibiotic resistance, which might drive their infection cycles and/or provide selective advantage to infected hosts. Exploring the groundwater virome provides a necessary foundation for integration of viruses into ecosystem models where they are key players in microbial adaption to environmental stress.IMPORTANCE To our knowledge, this is the first study to identify the bacteriophage distribution in a groundwater ecosystem shedding light on their prevalence and distribution across metal-contaminated and background sites. Our study is uniquely based on selective sequencing of solely the extrachromosomal elements of a microbiome followed by analysis for viral signatures, thus establishing a more focused approach for phage identifications. Using this method, we detected several novel phage genera along with those previously established. Our approach of using the whole-genome sequences of hundreds of bacterial isolates from the same site enabled us to make host assignments with high confidence, several at strain levels. Certain phage genes suggest that they provide an environment-specific selective advantage to their bacterial hosts. Our study lays the foundation for future research on directed phage isolations using specific bacterial host strains to further characterize groundwater phages, their life cycles, and their effects on groundwater microbiome and biogeochemistry.

ASIAN NIPAH VIRUS AND THE POTENTIAL OF NEW PANDEMIC

Nipah virus infection is a renewable threatening stage III zoonotic disease caused high mortality rates and significant public health risks in the past two decades. Several outbreaks of the Nipah virus occurred in Malaysia, Bangladesh, India and other Asian countries, which differed in the characteristics as each outbreak results from a novel strain of the virus. The continuous change of the viral hosts, as it jumps from bats to the animal/human and vice versa, but the virus in need to adapt to the new environment and favor mutations accuracy. The recent outbreaks of the virus caused much concern worldwide due to its ease of transmission and high mortality rates. During the rapid spread and replication of Nipah virus, more mutations are likely to develop, enhancing its epidemiological patterns and increasing its pathogenicity, raising the risk for a new pandemic. This review presents the chronological development of Nipah virus outbreaks and the main differences from the originally discovered Nipah virus and the more recent strains and discussed the potential of this virus to become a new pandemic.

Pollinator community species richness dilutes prevalence of multiple viruses within multiple host species.

Most pathogens are embedded in complex communities composed of multiple interacting hosts, but we are still learning how community-level factors, such as host diversity, abundance, and composition, contribute to pathogen spread for many host-pathogen systems. Evaluating relationships among multiple pathogens and hosts may clarify whether particular host or pathogen traits consistently drive links between community factors and pathogen prevalence. Pollinators are a good system to test how community composition influences pathogen spread because pollinator communities are extremely variable and contain several multi-host pathogens transmitted on shared floral resources. We conducted a field survey of four pollinator species to test the prevalence of three RNA viruses (deformed wing virus, black queen cell virus, and sacbrood virus) among pollinator communities with variable species richness, abundance, and composition. All three viruses showed a similar pattern of prevalence among hosts. Apis mellifera and Bombus impatiens had significantly higher viral prevalence than Lasioglossum spp. and Eucera pruinosa. In each species, lower virus prevalence was most strongly linked with greater pollinator community species richness. In contrast, pollinator abundance, species-specific pollinator abundance, and community composition were not associated with virus prevalence. Our results support a consistent dilution effect for multiple viruses and host species. Pollinators in species-rich communities had lower viral prevalence than pollinators from species-poor communities, when accounting for differences in pollinator abundance. Species-rich communities likely had lower viral prevalence because species-rich communities contained more native bee species likely to be poor viral hosts than species-poor communities, and all communities contained the highly competent hosts A. mellifera and B. impatiens. Interestingly, the strength of the dilution effect was not consistent among hosts. Instead, host species with low viral prevalence exhibited weaker dilution effects compared to hosts with high viral prevalence. Therefore, host species susceptibility and competence for each virus may contribute to variation in the strength of dilution effects. This study expands biodiversity-disease studies to the pollinator-virus system, finding consistent evidence of the dilution effect among multiple similar pathogens that infect "replicate" host communities.

Reservoir hosts prediction for COVID-19 by hybrid transfer learning model

The recent outbreak of COVID-19 has infected millions of people around the world, which is leading to the global emergency. In the event of the virus outbreak, it is crucial to get the carriers of the virus timely and precisely, then the animal origins can be isolated for further infection. Traditional identifications rely on fields and laboratory researches that lag the responses to emerging epidemic prevention. With the development of machine learning, the efficiency of predicting the viral hosts has been demonstrated by recent researchers. However, the problems of the limited annotated virus data and imbalanced hosts information restrict these approaches to obtain a better result. To assure the high reliability of predicting the animal origins on COVID-19, we extend transfer learning and ensemble learning to present a hybrid transfer learning model. When predicting the hosts of newly discovered virus, our model provides a novel solution to utilize the related virus domain as auxiliary to help building a robust model for target virus domain. The simulation results on several UCI benchmarks and viral genome datasets demonstrate that our model outperforms the general classical methods under the condition of limited target training sets and class-imbalance problems. By setting the coronavirus as target domain and other related virus as source domain, the feasibility of our approach is evaluated. Finally, we show the animal reservoirs prediction of the COVID-19 for further analysing.

Which species does the virus like most: Binding modes study between SARS-CoV-2 S protein and ACE2 receptor

BackgroundThe emergence of a novel coronavirus (SARS-CoV-2) has been spreading worldwide in 2020. Coronaviruses could mainly cause respiratory tract infections in humans and multiple system infections in many animals. The coronavirus enters the host cell through the binding of surface spike glycoprotein (S Protein) with host angiotensin-converting enzyme-Ⅱ (ACE2) protein. MethodsACE2 sequences of various species were aligned with human ACE2, accordingly, homology models for different species were constructed. Then, S-protein-ACE2 complexes were constructed using the generated homology models. The molecular dynamics simulations and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) were carried out to study the dynamical behavior of the generated S-ACE2 virtual complexes. Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF) and Radius of Gyration (Rg) were calculated to evaluate protein stability and compactness. ResultsThe binding free energies of S protein with ACE2 from Procyon lotor and Camelus dromedarius are about equal to that of humans. By comparing the free binding energies it were possible to identify potential viral hosts that could transmit the virus to human (risk of cross-species transmission). The predication showed that, besides human beings, SARS-CoV-2 may possibly infect Procyon lotor and Camelus dromedarius as well.

SARSCOVIDB-A New Platform for the Analysis of the Molecular Impact of SARS-CoV-2 Viral Infection.

The COVID-19 pandemic caused by the new coronavirus (SARS-CoV-2) has become a global emergency issue for public health. This threat has led to an acceleration in related research and, consequently, an unprecedented volume of clinical and experimental data that include changes in gene expression resulting from infection. The SARS-CoV-2 infection database (SARSCOVIDB: https://sarscovidb.org/) was created to mitigate the difficulties related to this scenario. The SARSCOVIDB is an online platform that aims to integrate all differential gene expression data, at messenger RNA and protein levels, helping to speed up analysis and research on the molecular impact of COVID-19. The database can be searched from different experimental perspectives and presents all related information from published data, such as viral strains, hosts, methodological approaches (proteomics or transcriptomics), genes/proteins, and samples (clinical or experimental). All information was taken from 24 articles related to analyses of differential gene expression out of 5,554 COVID-19/SARS-CoV-2-related articles published so far. The database features 12,535 genes whose expression has been identified as altered due to SARS-CoV-2 infection. Thus, the SARSCOVIDB is a new resource to support the health workers and the scientific community in understanding the pathogenesis and molecular impact caused by SARS-CoV-2.

Prokaryotic virus host predictor: a Gaussian model for host prediction of prokaryotic viruses in metagenomics

BackgroundViruses are ubiquitous biological entities, estimated to be the largest reservoirs of unexplored genetic diversity on Earth. Full functional characterization and annotation of newly discovered viruses requires tools to enable taxonomic assignment, the range of hosts, and biological properties of the virus. Here we focus on prokaryotic viruses, which include phages and archaeal viruses, and for which identifying the viral host is an essential step in characterizing the virus, as the virus relies on the host for survival. Currently, the method for determining the viral host is either to culture the virus, which is low-throughput, time-consuming, and expensive, or to computationally predict the viral hosts, which needs improvements at both accuracy and usability. Here we develop a Gaussian model to predict hosts for prokaryotic viruses with better performances than previous computational methods.ResultsWe present here Prokaryotic virus Host Predictor (PHP), a software tool using a Gaussian model, to predict hosts for prokaryotic viruses using the differences of k-mer frequencies between viral and host genomic sequences as features. PHP gave a host prediction accuracy of 34% (genus level) on the VirHostMatcher benchmark dataset and a host prediction accuracy of 35% (genus level) on a new dataset containing 671 viruses and 60,105 prokaryotic genomes. The prediction accuracy exceeded that of two alignment-free methods (VirHostMatcher and WIsH, 28–34%, genus level). PHP also outperformed these two alignment-free methods much (24–38% vs 18–20%, genus level) when predicting hosts for prokaryotic viruses which cannot be predicted by the BLAST-based or the CRISPR-spacer-based methods alone. Requiring a minimal score for making predictions (thresholding) and taking the consensus of the top 30 predictions further improved the host prediction accuracy of PHP.ConclusionsThe Prokaryotic virus Host Predictor software tool provides an intuitive and user-friendly API for the Gaussian model described herein. This work will facilitate the rapid identification of hosts for newly identified prokaryotic viruses in metagenomic studies.

EVIDENCE OF EPIZOOTIC HEMORRHAGIC DISEASE VIRUS AND BLUETONGUE VIRUS EXPOSURE IN NONNATIVE RUMINANT SPECIES IN NORTHERN FLORIDA.

Epizootic hemorrhagic disease virus (EHDV) and bluetongue virus (BTV) are vector-borne viruses of ruminants nearly worldwide. They can affect white-tailed deer (WTD; Odocoileus virginianus), the ranching industry, and nonindigenous hoof stock species managed for conservation. One potential risk factor for ranched WTD is commingling with nonindigenous species on high-fenced properties. Nonindigenous species provide novel viewing and hunting opportunities; however, their presence may create disease hazards. Furthermore, animals within conservation properties may be at a risk from commingling exotics and adjacent wild WTD. Currently, knowledge about EHDV and BTV seroprevalence and transmission is limited in nonindigenous populations in the southeastern United States. The authors conducted a serological survey of 10 Bovidae and 5 Cervidae species residing within two properties in northern Florida. The first site was a conservation property breeding threatened nonindigenous species for conservation. The second property was a private high-fenced game preserve managing WTD and nonindigenous species for breeding, sale, and harvest. Blood samples were tested for titers to three EHDV serotypes (1, 2, and 6) and active circulating viral EHDV and BTV. The private ranch had evidence of EHDV or BTV in one of three (33.3%) Bovidae species and four of five (80%) Cervidae species sampled. At the conservation property, evidence of EHDV infection was found in four of seven (57.1%) Bovidae and one of one (100%) Cervidae species sampled. The presence of antibodies in many nonindigenous species sampled might indicate these species are potential viral hosts and may be a risk to ranched WTD and other species within the same property. Nonindigenous species within the private ranch and conservation properties are at risk of contracting EHDV and BTV, and herd managers should reduce vector-host interactions and consider increased biosecurity measures when translocating animals.

Serological evidence of West Nile virus infection among birds and horses in some geographical locations of Iran.

Recent expansion of arboviruses such as West Nile (WNV), Usutu (USUV), and tick‐borne encephalitis (TBEV) over their natural range of distribution needs strengthening their surveillance. As common viral vertebrate hosts, birds and horses deserve special attention with routine serological surveillance. Here, we estimated the seroprevalence of WNV, USUV and TBEV in 160 migrating/resident birds and 60 horses sampled in Mazandaran, Golestan, North Khorasan, Kordestan provinces and Golestan province of Iran respectively. ELISA results showed that of 220 collected samples, 32 samples (14.54%), including 22 birds and 10 horses, were positive. Microsphere immunoassay results showed that 16.7% (10/60) of horse blood samples collected in Golestan province were seropositive against WNV (7; 11.7%), Flavivirus (2; 3.3%) and seropositive for USUV or WNV (1; 1.7%). Furthermore, micro virus neutralization tests revealed that four of seven ELISA‐positive bird blood samples were seropositive against WNV: two Egyptian vultures, and one long‐legged buzzard collected in Golestan province as well as a golden eagle collected in North Khorasan province. No evidence of seropositivity with TBEV was observed in collected samples. We showed that WNV, responsible for neuroinvasive infection in vertebrates, is circulating among birds and horses in Iran, recommending a sustained surveillance of viral infections in animals, and anticipating future infections in humans.

Human coronaviruses with emphasis on the COVID-19 outbreak.

Human coronaviruses are known as respiratory pathogens mainly associated with a range of respiratory diseases. In the past 18 years, the beginning of severe acute respiratory syndrome human coronavirus (SARS-HCoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and now the (COVID-19) have driven the HCoV into the platform of the scientific community due to their high pathogenicity in humans. Our study about the HCoV has contributed extensively to the understanding of HCoV pathogenesis its outbreak and precautionary measurements mainly COVID-19. By the 16-February 2020, total existing diagnosis cases of COVID-19, in china now numbered around 57,255, total cumulative diagnosis is about 68,592, total existing suspicion is about 8228, a total severe existing disease 11,272, the total cumulative cure is about 9671 with more than 1666 cumulative deaths have been reported. The purpose of the review is to summarize the present knowledge on the viral diversity, reservoir hosts, and geographical distributions of Human coronavirus (COVID-19) in China.

Discovery of potential multi-target-directed ligands by targeting host-specific SARS-CoV-2 structurally conserved main protease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in the current COVID-19 pandemic. Worldwide this disease has infected over 2.5 million individuals with a mortality rate ranging from 5 to 10%. There are several efforts going on in the drug discovery to control the SARS-CoV-2 viral infection. The main protease (MPro) plays a critical role in viral replication and maturation, thus can serve as the primary drug target. To understand the structural evolution of MPro, we have performed phylogenetic and Sequence Similarity Network analysis, that depicted divergence of Coronaviridae MPro in five clusters specific to viral hosts. This clustering was corroborated with the comparison of MPro structures. Furthermore, it has been observed that backbone and binding site conformations are conserved despite variation in some of the residues. These attributes can be exploited to repurpose available viral protease inhibitors against SARS-CoV-2 MPro. In agreement with this, we performed screening of ∼7100 molecules including active ingredients present in the Ayurvedic anti-tussive medicines, anti-viral phytochemicals and synthetic anti-virals against SARS-CoV-2 MPro as the primary target. We identified several natural molecules like δ-viniferin, myricitrin, taiwanhomoflavone A, lactucopicrin 15-oxalate, nympholide A, afzelin, biorobin, hesperidin and phyllaemblicin B that strongly binds to SARS-CoV-2 MPro. Intrestingly, these molecules also showed strong binding with other potential targets of SARS-CoV-2 infection like viral receptor human angiotensin-converting enzyme 2 (hACE-2) and RNA dependent RNA polymerase (RdRp). We anticipate that our approach for identification of multi-target-directed ligand will provide new avenues for drug discovery against SARS-CoV-2 infection.Communicated by Ramaswamy H. Sarma

The Virophage Family Lavidaviridae

Double-stranded (ds) DNA viruses of the family Lavidaviridae, commonly known as virophages, are a fascinating group of eukaryotic viruses that depend on a coinfecting giant dsDNA virus of the Mimiviridae for their propagation. Instead of replicating in the nucleus, virophages multiply in the cytoplasmic virion factory of a coinfecting giant virus inside a phototrophic or heterotrophic protistal host cell. Virophages are parasites of giant viruses and can inhibit their replication, which may lead to increased survival rates of the infected host cell population. The genomes of virophages are 17-33 kilobase pairs (kbp) long and encode 16-34 proteins. Genetic signatures of virophages can be found in metagenomic datasets from various saltwater and freshwater environments around the planet. Most virophages share a set of conserved genes that code for a major and a minor capsid protein, a cysteine protease, a genome-packaging ATPase, and a superfamily 3 helicase, although the genomes are otherwise diverse and variable. Lavidaviruses share genes with other mobile genetic elements, suggesting that horizontal gene transfer and recombination have been major forces in shaping these viral genomes. Integrases are occasionally found in virophage genomes and enable these DNA viruses to persist as provirophages in the chromosomes of their viral and cellular hosts. As we watch the genetic diversity of this new viral family unfold through metagenomics, additional isolates are still lacking and critical questions regarding their infection cycle, host range, and ecology remain to be answered.

HIV-1 Balances the Fitness Costs and Benefits of Disrupting the Host Cell Actin Cytoskeleton Early after Mucosal Transmission

HIV-1 primarily infects T lymphocytes and uses these motile cells as migratory vehicles for effective dissemination in the host. Paradoxically, the virus at the same time disrupts multiple cellular processes underlying lymphocyte motility, seemingly counterproductive to rapid systemic infection. Here we show by intravital microscopy in humanized mice that perturbation of the actin cytoskeleton via the lentiviral protein Nef, and not changes to chemokine receptor expression or function, is the dominant cause of dysregulated infected Tcell motility in lymphoid tissue by preventing stable cellular polarization required for fast migration. Accordingly, disrupting the Nef hydrophobic patch that facilitates actin cytoskeletal perturbation initially accelerates systemic viral dissemination after female genital transmission. However, the same feature of Nef was subsequently critical for viral persistence inimmune-competent hosts. Therefore, a highly conserved activity of lentiviral Nef proteins has dual effects and imposes both fitness costs and benefits on the virus at different stages of infection.

Total body CD4+ T cell dynamics in treated and untreated SIV infection revealed by in vivo imaging

The peripheral blood represents only a small fraction of the total number of lymphocytes in the body. To develop a more thorough understanding of T cell dynamics, including the effects of SIV/SHIV/HIV infection on immune cell depletion and immune reconstitution following combination antiretroviral therapy (cART), one needs to utilize approaches that allow direct visualization of lymphoid tissues. In the present study, noninvasive in vivo imaging of the CD4+ T cell pool has revealed that the timing of the CD4+ T cell pool reconstitution following initiation of ART in SIV-infected nonhuman primates (NHPs) appears seemingly stochastic among clusters of lymph nodes within the same host. At 4 weeks following initiation or interruption of cART, the changes observed in peripheral blood (PB) are primarily related to changes in the whole-body CD4 pool rather than changes in lymphocyte trafficking. Lymph node CD4 pools in long-term antiretroviral-treated and plasma viral load-suppressed hosts appear suboptimally reconstituted compared with healthy controls, while splenic CD4 pools appear similar between the 2 groups.