Search Results (16)

The bacterial genus Wolbachia induces reproductive abnormalities in its insect host, including cytoplasmic incompatibility (CI), which causes embryonic death in the crossing of infected males and uninfected females. Hence, Wolbachia-based strategies are employed to control insect pests. However, Wolbachia does not naturally infect Matsumuratettix hiroglyphicus (Matsumura), the main vector of the phytoplasma causing the sugarcane white leaf (SCWL) disease. In this study, the wYfla Wolbachia strain, which induces strong CI in its original host, was microinjected into nymphs of M. hiroglyphicus. Molecular detection revealed that Wolbachia was successfully transinfected into the recipient host, with an infection frequency of 55–80% in up to eight generations after transinfection. Wolbachia exhibited no significant detrimental effects on the developmental time of the immature stages, adult emergences, and female longevity, whereas the lifespan of transinfected males was decreased. Reciprocal crossing revealed that Wolbachia infection did not affect the number of eggs laid per female. However, the hatching rate produced by the pairs between the transinfected males and naturally uninfected females significantly decreased. The evidence of Wolbachia transmitted through the generations tested and partial CI occurrence in transinfected M. hiroglyphicus highlights the possibility of the future development of Wolbachia-based strategies for controlling the vector of SCWL. Full article

Co-infection or superinfection of the host by two or more virus species is a common event, potentially leading to viral interference, viral synergy, or neutral interaction. The simultaneous presence of two or more viruses, even distantly related, within the same cell depends upon viral tropism, i.e., the entry of viruses via receptors present on the same cell type. Subsequently, productive infection depends on the ability of these viruses to replicate efficiently in the same cellular environment. HIV-1 initially targets CCR5-expressing tissue memory CD4⁺ T cells, and in the absence of early cART initiation, a co-receptor switch may occur, leading to the infection of naïve and memory CXCR4-expressing CD4⁺ T cells. HIV-1 infection of macrophages at the G₁ stage of their cell cycle also occurs in vivo, broadening the possible occurrence of co-infections between HIV-1 and other viruses at the cellular level. Moreover, HIV-1-infected DCs can transfer the virus to CD4⁺ T cells via trans-infection. This review focuses on the description of reported co-infections within the same cell between HIV-1 and other human pathogenic, non-pathogenic, or low-pathogenic viruses, including HIV-2, HTLV, HSV, HHV-6/-7, GBV-C, Dengue, and Ebola viruses, also discussing the possible reciprocal interactions in terms of virus replication and virus pseudotyping. Full article

The intracellular bacterium Wolbachia is increasingly being utilised in control programs to limit the spread of arboviruses by Aedes mosquitoes. Achieving a better understanding of how Wolbachia strains can reduce viral replication/spread could be important for the long-term success of such programs. Previous studies have indicated that for some strains of Wolbachia, perturbations in lipid metabolism and cholesterol storage are vital in Wolbachia-mediated antiviral activity against the flaviviruses dengue and Zika; however, it has not yet been examined whether arboviruses in the alphavirus group are affected in the same way. Here, using the reporters for the alphavirus Semliki Forest virus (SFV) in Aedes albopictus cells, we found that Wolbachia strains wMel, wAu and wAlbB blocked viral replication/translation early in infection and that storage of cholesterol in lipid droplets is not key to this inhibition. Another alphavirus, o’nyong nyong virus (ONNV), was tested in both Aedes albopictus cells and in vivo in stable, transinfected Aedes aegypti mosquito lines. The strains wMel, wAu and wAlbB show strong antiviral activity against ONNV both in vitro and in vivo. Again, 2-hydroxypropyl-β-cyclodextrin (2HPCD) was not able to rescue ONNV replication in cell lines, suggesting that the release of stored cholesterol caused by wMel is not able to rescue blockage of ONNV. Taken together, this study shows that alphaviruses appear to be inhibited early in replication/translation and that there may be differences in how alphaviruses are inhibited by Wolbachia in comparison to flaviviruses. Full article

The barley yellow dwarf virus (BYDV) of cereals is thought to substantially increase the high-temperature tolerance of its aphid vector, Rhopalosiphum padi, which may enhance its transmission efficiency. This is based on experiments with North American strains of BYDV and R. padi. Here, we independently test these by measuring the temperature tolerance, via Critical Thermal Maximum (CTmax) and knockdown time, of Australian R. padi infected with a local BYDV isolate. We further consider the interaction between BYDV transmission, the primary endosymbiont of R. padi (Buchnera aphidicola), and a transinfected secondary endosymbiont (Rickettsiella viridis) which reduces the thermotolerance of other aphid species. We failed to find an increase in tolerance to high temperatures in BYDV-infected aphids or an impact of Rickettsiella on thermotolerance. However, BYDV interacted with R. padi endosymbionts in unexpected ways, suppressing the density of Buchnera and Rickettsiella. BYDV density was also fourfold higher in Rickettsiella-infected aphids. Our findings indicate that BYDV does not necessarily increase the temperature tolerance of the aphid transmission vector to increase its transmission potential, at least for the genotype combinations tested here. The interactions between BYDV and Rickettsiella suggest new ways in which aphid endosymbionts may influence how BYDV spreads, which needs further testing in a field context. Full article

Although COVID-19 transmission has been reduced by the advent of vaccinations and a variety of rapid monitoring techniques, the SARS-CoV-2 virus itself has shown a remarkable ability to mutate and persist. With this long track record of immune escape, researchers are still exploring prophylactic treatments to curtail future SARS-CoV-2 variants. Specifically, much focus has been placed on the antiviral lectin Griffithsin in preventing spike protein-mediated infection via the hACE2 receptor (direct infection). However, an oft-overlooked aspect of SARS-CoV-2 infection is viral capture by attachment receptors such as DC-SIGN, which is thought to facilitate the initial stages of COVID-19 infection in the lung tissue (called trans-infection). In addition, while immune escape is dictated by mutations in the spike protein, coronaviral virions also incorporate M, N, and E structural proteins within the particle. In this paper, we explored how several structural facets of both the SARS-CoV-2 virion and the antiviral lectin Griffithsin can affect and attenuate the infectivity of SARS-CoV-2 pseudovirus. We found that Griffithsin was a better inhibitor of hACE2-mediated direct infection when the coronaviral M protein is present compared to when it is absent (possibly providing an explanation regarding why Griffithsin shows better inhibition against authentic SARS-CoV-2 as opposed to pseudotyped viruses, which generally do not contain M) and that Griffithsin was not an effective inhibitor of DC-SIGN-mediated trans-infection. Furthermore, we found that DC-SIGN appeared to mediate trans-infection exclusively via binding to the SARS-CoV-2 spike protein, with no significant effect observed when other viral proteins (M, N, and/or E) were present. These results provide etiological data that may help to direct the development of novel antiviral treatments, either by leveraging Griffithsin binding to the M protein as a novel strategy to prevent SARS-CoV-2 infection or by narrowing efforts to inhibit trans-infection to focus on DC-SIGN binding to SARS-CoV-2 spike protein. Full article

Antiretroviral therapy (ART) provides an effective method for managing HIV-1 infection and preventing the onset of AIDS; however, it is ineffective against the reservoir of latent HIV-1 that persists predominantly in resting CD4⁺ T cells. Understanding the mechanisms that facilitate the persistence of the latent reservoir is key to developing an effective cure for HIV-1. Of particular importance in the establishment and maintenance of the latent viral reservoir is the intercellular transfer of HIV-1 from professional antigen-presenting cells (APCs—monocytes/macrophages, myeloid dendritic cells, and B lymphocytes) to CD4⁺ T cells, termed trans-infection. Whereas virus-to-cell HIV-1 cis infection is sensitive to ART, trans-infection is impervious to antiviral therapy. APCs from HIV-1-positive non-progressors (NPs) who control their HIV-1 infection in the absence of ART do not trans-infect CD4⁺ T cells. In this review, we focus on this unique property of NPs that we propose is driven by a genetically inherited, altered cholesterol metabolism in their APCs. We focus on cellular cholesterol homeostasis and the role of cholesterol metabolism in HIV-1 trans-infection, and notably, the link between cholesterol efflux and HIV-1 trans-infection in NPs. Full article

The SARS-CoV-2 virion has shown remarkable resilience, capable of mutating to escape immune detection and re-establishing infectious capabilities despite new vaccine rollouts. Therefore, there is a critical need to identify relatively immutable epitopes on the SARS-CoV-2 virion that are resistant to future mutations the virus may accumulate. While hACE2 has been identified as the receptor that mediates SARS-CoV-2 susceptibility, it is only modestly expressed in lung tissue. C-type lectin receptors like DC-SIGN can act as attachment sites to enhance SARS-CoV-2 infection of cells with moderate or low hACE2 expression. We developed an easy-to-implement assay system that allows for the testing of SARS-CoV-2 trans-infection. Using our assay, we assessed how SARS-CoV-2 Spike S1-domain glycans and spike proteins from different strains affected the ability of pseudotyped lentivirions to undergo DC-SIGN-mediated trans-infection. Through our experiments with seven glycan point mutants, two glycan cluster mutants and four strains of SARS-CoV-2 spike, we found that glycans N17 and N122 appear to have significant roles in maintaining COVID-19′s infectious capabilities. We further found that the virus cannot retain infectivity upon the loss of multiple glycosylation sites, and that Omicron BA.2 pseudovirions may have an increased ability to bind to other non-lectin receptor proteins on the surface of cells. Taken together, our work opens the door to the development of new therapeutics that can target overlooked epitopes of the SARS-CoV-2 virion to prevent C-type lectin-receptor-mediated trans-infection in lung tissue. Full article

Macrophages (Mø) and dendritic cells (DCs) are key players in human immunodeficiency virus (HIV) infection and pathogenesis. They are essential for the spread of HIV to CD4+ T lymphocytes (TCD4+) during acute infection. In addition, they constitute a persistently infected reservoir in which viral production is maintained for long periods of time during chronic infection. Defining how HIV interacts with these cells remains a critical area of research to elucidate the pathogenic mechanisms of acute spread and sustained chronic infection and transmission. To address this issue, we analyzed a panel of phenotypically distinct HIV-1 and HIV-2 primary isolates for the efficiency with which they are transferred from infected DCs or Mø to TCD4+. Our results show that infected Mø and DCs spread the virus to TCD4+ via cell-free viral particles in addition to other alternative pathways. We demonstrate that the production of infectious viral particles is induced by the co-culture of different cell populations, indicating that the contribution of cell signaling driven by cell-to-cell contact is a trigger for viral replication. The results obtained do not correlate with the phenotypic characteristics of the HIV isolates, namely their co-receptor usage, nor do we find significant differences between HIV-1 and HIV-2 in terms of cis- or trans-infection. The data presented here may help to further elucidate the cell-to-cell spread of HIV and its importance in HIV pathogenesis. Ultimately, this knowledge is critical for new therapeutic and vaccine approaches. Full article

HIV-1 cell-to-cell transmission is key for an effective viral replication that evades immunity. This highly infectious mechanism is orchestrated by different cellular targets that utilize a wide variety of processes to efficiently transfer HIV-1 particles. Dendritic cells (DCs) are the most potent antigen presenting cells that initiate antiviral immune responses, but are also the cells with highest capacity to transfer HIV-1. This mechanism, known as trans-infection, relies on the capacity of DCs to capture HIV-1 particles via lectin receptors such as the sialic acid-binding I-type lectin Siglec-1/CD169. The discovery of the molecular interaction of Siglec-1 with sialylated lipids exposed on HIV-1 membranes has enlightened how this receptor can bind to several enveloped viruses. The outcome of these interactions can either mount effective immune responses, boost the productive infection of DCs and favour innate sensing, or fuel viral transmission via trans-infection. Here we review these scenarios focusing on HIV-1 and other enveloped viruses such as Ebola virus or SARS-CoV-2. Full article

The field release of Wolbachia trans-infected male mosquitoes, as well as the use of toxic sugar baits, is a novel and promising candidate technique for integrated mosquito management programs. However, the methods of action of the two techniques may not be complementary, because the Wolbachia method releases mosquitoes into the environment expecting a wild population reduction in subsequent generations while the toxic baits are intended to reduce the wild population by killing mosquitoes. This laboratory study was conducted to evaluate the effectiveness of boric acid toxic sugar baits on Wolbachia trans-infected male Aedes albopictus, relative to wild-type Ae. albopictus males. Wolbachia trans-infected (ZAP male^®) and the wild-type Ae. albopictus males were exposed separately to 1% boric acid in a 10% sucrose solution in BugDorms. In the control test, the two groups were exposed to 10% sucrose solution without boric acid. Percent mortalities were counted for 24 h, 48 h and 72 h post exposure periods. The results show that 1% boric acid toxic sugar bait can effectively kill ZAP males under laboratory conditions, and the effectiveness was significantly higher after 24 h and 48 h, compared to wild-type male Ae. albopictus. This finding will help in planning and coordinating integrated mosquito management programs, including both Wolbachia trans-infected mosquito releases and the use of toxic sugar baits against Ae. albopictus. Full article

Nascent HIV-1 particles incorporate the viral envelope glycoprotein and multiple host transmembrane proteins during assembly at the plasma membrane. At least some of these host transmembrane proteins on the surface of virions are reported as pro-viral factors that enhance virus attachment to target cells or facilitate trans-infection of CD4⁺ T cells via interactions with non-T cells. In addition to the pro-viral factors, anti-viral transmembrane proteins are incorporated into progeny virions. These virion-incorporated transmembrane proteins inhibit HIV-1 entry at the point of attachment and fusion. In infected polarized CD4⁺ T cells, HIV-1 Gag localizes to a rear-end protrusion known as the uropod. Regardless of cell polarization, Gag colocalizes with and promotes the virion incorporation of a subset of uropod-directed host transmembrane proteins, including CD162, CD43, and CD44. Until recently, the functions of these virion-incorporated proteins had not been clear. Here, we review the recent findings about the roles played by virion-incorporated CD162, CD43, and CD44 in HIV-1 spread to CD4⁺ T cells. Full article

Tuberculosis (TB) is the leading cause of death among HIV-1-infected individuals and Mycobacterium tuberculosis (Mtb) co-infection is an early precipitate to AIDS. We aimed to determine whether Mtb strains differentially modulate cellular susceptibility to HIV-1 infection (cis- and trans-infection), via surface receptor interaction by their cell envelope lipids. Total lipids from pathogenic (lineage 4 Mtb H37Rv, CDC1551 and lineage 2 Mtb HN878, EU127) and non-pathogenic (Mycobacterium bovis BCG and Mycobacterium smegmatis) Mycobacterium strains were integrated into liposomes mimicking the lipid distribution and antigen accessibility of the mycobacterial cell wall. The resulting liposomes were tested for modulating in vitro HIV-1 cis- and trans-infection of TZM-bl cells using single-cycle infectious virus particles. Mtb glycolipids did not affect HIV-1 direct infection however, trans-infection of both R5 and X4 tropic HIV-1 strains were impaired in the presence of glycolipids from M. bovis, Mtb H37Rv and Mtb EU127 strains when using Raji-DC-SIGN cells or immature and mature dendritic cells (DCs) to capture virus. SL1, PDIM and TDM lipids were identified to be involved in DC-SIGN recognition and impairment of HIV-1 trans-infection. These findings indicate that variant strains of Mtb have differential effect on HIV-1 trans-infection with the potential to influence HIV-1 disease course in co-infected individuals. Full article

Buffalo flies, Haematobia (irritans) exigua (BF), are obligate haematophagous ectoparasites of cattle that cause significant economic and welfare impacts in northern Australian cattle. With climate change and the development of resistance to commonly used chemicals, BF are rapidly spreading southwards. Wolbachia is a maternally transmitted bacterial endosymbiont of insects that induces a range of effects on its host, including cytoplasmic incompatibility (male sterility), reduced fitness, and inhibition of pathogen transmission. We are examining the potential for use of Wolbachia in area-wide control of BF. Following a survey of Australian BF populations that showed Wolbachia was not present, we have tested embryonic microinjection, pupal injection and injection of adults as a first step towards the development of a Wolbachia infected BF line. Here we report distribution and growth of Wolbachia in somatic and germline tissue of BF injected with the three Wolbachia strains; wAlbB, wMel and wMelPop. Our results to date suggest that pupal or adult injection may be a more suitable method for transinfecting BF than embryonic microinjection. We also demonstrate Wolbachia induced fitness effects in injected BF including shortened lifespan, decreased pupal emergence, and reduced egg production. Future work will focus on establishing a stably infected BF strain, towards the design of Wolbachia-based control programs for BF. Full article

Globally, the dengue viruses (DENVs) infect approximately 300 million people annually. Australia has a history of epidemic dengue, with outbreaks in the early decades of the twentieth century responsible for tens of thousands of cases. Seminal experiments conducted by Australian scientists during these outbreaks were the first to incriminate Aedes aegypti as a major vector of dengue viruses. One hundred years later, Australian scientists are playing a lead role in the development of surveillance and suppression strategies that target this mosquito species. Surveillance of Ae. aegypti populations and their associated dengue risk was greatly improved by understanding the contribution of key premises, key containers, and cryptic larval habitats to mosquito productivity, and, more recently, the development of novel adult traps. In terms of mosquito control, targeted indoor residual pyrethroid spraying and community-based biological control utilizing predatory copepods can significantly reduce Ae. aegypti populations. The release of Ae. aegypti transinfected with the virus-blocking bacterium, Wolbachia, provides a promising strategy for limiting DENV transmission. These diverse strategies developed by Australian scientists have the potential to alleviate the burden of dengue in the future, whether it is at the local level or as part of a country-wide program. Full article

Aedes albopictus is a major vector of dengue (DENV) and chikungunya (CHIKV) viruses, causing millions of infections annually. It naturally carries, at high frequency, the intracellular inherited bacterial endosymbiont Wolbachia strains wAlbA and wAlbB; transinfection with the higher-density Wolbachia strain wMel from Drosophila melanogaster led to transmission blocking of both arboviruses. The hypothesis that reactive oxygen species (ROS)-induced immune activation plays a role in arbovirus inhibition in this species was examined. In contrast to previous observations in Ae. aegypti, elevation of ROS levels was not observed in either cell lines or mosquito lines carrying the wild-type Wolbachia or higher-density Drosophila Wolbachia strains. There was also no upregulation of genes controlling innate immune pathways or with antioxidant/ROS-producing functions. These data suggest that ROS-mediated immune activation is not an important component of the viral transmission-blocking phenotype in this species. Full article