Remorins are plant-specific membrane-associated proteins and were proposed to play crucial roles in plant-pathogen interactions. However, little is known about how pathogens counter remorin-mediated host responses. In this study, by quantitative whole-proteome analysis we found that the remorin protein (NbREM1) is downregulated early in Rice stripe virus (RSV) infection. We further discovered that the turnover of NbREM1 is regulated by S-acylation modification and its degradation is mediated mainly through the autophagy pathway. Interestingly, RSV can interfere with the S-acylation of NbREM1, which is required to negatively regulate RSV infection by restricting virus cell-to-cell trafficking. The disruption of NbREM1 S-acylation affects its targeting to the plasma membrane microdomain, and the resulting accumulation of non-targeted NbREM1 is subjected to autophagic degradation, causing downregulation of NbREM1. Moreover, we found that RSV-encoded movement protein, NSvc4, alone can interfere with NbREM1 S-acylation through binding with the C-terminal domain of NbREM1 the S-acylation of OsREM1.4, the homologous remorin of NbREM1, and thus remorin-mediated defense against RSV in rice, the original host of RSV, indicating that downregulation of the remorin protein level by interfering with its S-acylation is a common strategy adopted by RSV to overcome remorin-mediated inhibition of virus movement.

BackgroundSmall RNA-mediated gene silencing plays evolutionarily conserved roles in gene regulation and defense against invasive nucleic acids. Virus-derived small interfering RNAs (vsiRNAs) are one of the key elements involved in RNA silencing-based antiviral activities in plant and insect. vsiRNAs produced after viruses infecting hosts from a single kingdom (i.e., plant or animal) are well described. In contrast, vsiRNAs derived from viruses capable of infecting both plants and their insect vectors have not been characterized.Methodology/Principal FindingsWe examined Rice stripe virus (RSV)-derived small interfering RNAs in three different hosts, Oryza sativa, Nicotiana benthamiana and a natural RSV transmitting vector Laodelphgax striatellus, through deep sequencing. Our results show that large amounts of vsiRNAs generated in these hosts after RSV infection. The vsiRNAs from N. benthamiana and L. striatellus mapped equally to the genomic- and antigenomic-strand of RSV RNAs. They showed, however, a significant bias in those from O. sativa. Furthermore, our results demonstrate that the number and size distributions of vsiRNAs in the three hosts were very different. In O. sativa and N. benthamiana, most vsiRNAs were mapped to the discrete regions in the RSV genome sequence, and most of the vsiRNAs from these two hosts were generated from RSV genomic RNAs 3 and 4. In contrast, the vsiRNAs identified in L. striatellus distributed uniformly along the whole genome of RSV. We have also shown that silencing Agronaute 2 in L. striatellus enhanced RSV accumulation in this host.Conclusions/SignificanceOur study demonstrates that the core RNA-induced gene silencing (RNAi) machinery is present in L. striatellus. We also provide evidence that the RNAi-mediated immunity against RSV is present in L. striatellus. We propose that a common small RNA-mediated virus defense mechanism exists in both helipterum insects and plants, but the vsiRNAs are generated differentially in different hosts.

Natural killer (NK) cells are important for maintenance of innate immune system stability and serve as a first line of defense against tumors and virus infections; they can act either directly or indirectly and are regulated via co-operation between inhibitory and stimulatory surface receptors. The recently reported inhibitory receptor, TIGIT, can be expressed on the NK cell surface; however, the expression level and function of TIGIT on NK cells during HIV infection is unknown. In this study, for the first time, we investigated the expression and function of TIGIT in NK cells from HIV-infected individuals. Our data demonstrate that the level of TIGIT is higher on NK cells from patients infected with human immunodeficiency virus (HIV) compared with HIV-negative healthy controls. TIGIT expression is inversely correlated with CD4+ T cell counts and positively correlated with plasma viral loads. Additionally, levels of the TIGIT ligand, CD155, were higher on CD4+ T cells from HIV-infected individuals compared with those from healthy controls; however, there was no difference in the level of the activating receptor, CD226, which recognizes the same ligands as TIGIT. Furthermore, TIGIT was found to specifically up-regulated on CD226+ NK cells in HIV-infected individuals, and either rIL-10, or rIL-12 + rIL-15, could induce TIGIT expression on these cells. In addition, high TIGIT expression inhibited the production of interferon-gamma (IFN-γ) by NK cells, while TIGIT inhibition restored IFN-γ production. Overall, these results highlight the important role of TIGIT in NK cell function and suggest a potential new avenue for the development of therapeutic strategies toward a functional cure for HIV.

Rice stripe disease caused by Rice stripe virus (RSV) is one of the most devastating plant viruses of rice and causes enormous losses in production. RSV is transmitted from plant to plant by the small brown planthopper ( Laodelphax striatellus) in a circulative–propagative manner. The recent reemergence of this pathogen in East Asia since 2000 has made RSV one of the most studied plant viruses over the past two decades. Extensive studies of RSV have resulted in substantial advances regarding fundamental aspects of the virus infection. Here, we compile and analyze recent information on RSV with a special emphasis on the strategies that RSV has adopted to establish infections. These advances include RSV replication and movement in host plants and the small brown planthopper vector, innate immunity defenses against RSV infection, epidemiology, and recent advances in the management of rice stripe disease. Understanding these issues will facilitate the design of novel antiviral therapies for management and contribute to a more detailed understanding of negative-sense virus–host interactions at the molecular level. Expected final online publication date for the Annual Review of Phytopathology, Volume 59 is August 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Natural killer (NK) cells are the first line of defense against pathogens of the immune system and also play an important role in resistance against HIV. The activating receptor NKG2C and the inhibitory receptor NKG2A co-modulate the function of NK cells by recognizing the same ligand, HLA-E. However, the role of NKG2A and NKG2C on viral set point and the prediction of HIV disease progression have been rarely reported. In this study, we determined the expression of NKG2C or NKG2A on the surface of NK cells from 22 individuals with primary HIV infection (PHI) stage and 23 HIV-negative normal control (NC) subjects. The CD4+ T cell count and plasma level of HIV RNA in the infected individuals were longitudinally followed-up for about 720 days. The proportion of NKG2C+NKG2A− NK cells was higher in subjects from the low set point group and was negatively correlated with the viral load. In addition, strong anti-HIV activities were observed in NKG2C+ NK cells from the HIV-positive donors. Furthermore, a proportion of NKG2C+NKG2A− NK cells >35.45%, and a ratio of NKG2C/NKG2A >1.7 were predictive for higher CD4+ T cell counts 720 days after infection. Collectively, the experimental results allow us to draw the conclusion that NKG2C+ NK cells might exert an antiviral effect and that the proportion of NKG2C+NKG2A− NK cells, and the ratio of NKG2C/NKG2A, are potential biomarkers for predicting HIV disease progression.

The ubiquitin/26S proteasome system plays a vital role in regulating host defenses against pathogens. Previous studies have highlighted different roles for the ubiquitin/26S proteasome in defense during virus infection in both mammals and plants, but their role in the vectors that transmit those viruses is still unclear. In this study, we determined that the 26S proteasome is present in the small brown planthopper (SBPH) (Laodelphgax striatellus) and has components similar to those in plants and mammals. There was an increase in the accumulation of Rice stripe virus (RSV) in the transmitting vector SBPH after disrupting the 26S proteasome, indicating that the SBPH 26S proteasome plays a role in defense against RSV infection by regulating RSV accumulation. Yeast two-hybrid analysis determined that a subunit of the 26S proteasome, named RPN3, could interact with RSV NS3. Transient overexpression of RPN3 had no effect on the RNA silencing suppressor activity of RSV NS3. However, NS3 could inhibit the ability of SBPH rpn3 to complement an rpn3 mutation in yeast. Our findings also indicate that the direct interaction between RPN3 and NS3 was responsible for inhibiting the complementation ability of RPN3. In vivo, we found an accumulation of ubiquitinated protein in SBPH tissues where the RSV titer was high, and silencing of rpn3 resulted in malfunction of the SBPH proteasome-mediated proteolysis. Consequently, viruliferous SBPH in which RPN3 was repressed transmitted the virus more effectively as a result of higher accumulation of RSV. Our results suggest that the RSV NS3 protein is able to hijack the 26S proteasome in SBPH via a direct interaction with the RPN3 subunit to attenuate the host defense response. IMPORTANCEWe show, for the first time, that the 26S proteasome components are present in the small brown planthopper and play a role in defense against its vectored plant virus (RSV). In turn, RSV encodes a protein that subverts the SBPH 26S proteasome via direct interaction with the 26S proteasome subunit RPN3. Our results imply that the molecular arms race observed in plant hosts can be extended to the insect vector that transmits those viruses. Rice stripe virus (RSV), one of the most destructive pathogens of rice production, has been responsible for numerous epidemics since it was first described in Japan in 1897 (1-3). RSV is the type member of the Tenuivirus genus, and the viral genome consists of four single-stranded RNA segments which range in size from approximately 8.9 to 2.1 kb (4, 5). RNA 1 is negative sense and encodes a putative RNA-dependent RNA polymerase. RNAs 2, 3, and 4 are ambisense, and each contains two open reading frames (ORFs), with one on the viral RNA strand (vRNA) and the second on the viral cRNA strand (vcRNA) (6). RSV vRNA 2 encodes a membrane-associated protein that reportedly is an RNA silencing suppressor and interacts with suppressor of gene silencing 3 (SGS3) (7). vcRNA 2 encodes a glycoprotein (NSvc2) which when expressed in insect cells is displayed on the membrane su...

We demonstrate an HIV-mediated dysregulation of cofilin in CD4 T cells and propose therapeutics to restore T cell motility.

The plant genome can produce long non-coding RNAs (lncRNAs), some of which have been identified as important regulators of gene expression. To better understand the response mechanism of rice plants to Rice black-streaked dwarf virus (RBSDV) infection, we performed a comparative transcriptome analysis between the RBSDV-infected and non-infected rice plants. A total of 1342 mRNAs and 22 lncRNAs were identified to be differentially expressed after RBSDV infection. Most differentially expressed transcripts involved in the plant–pathogen interaction pathway were upregulated after RBSDV infection, indicating the activation of rice defense response by RBSDV. A network of differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) was then constructed. In this network, there are 56 plant–pathogen interaction-related DEmRNAs co-expressing with 20 DElncRNAs, suggesting these DElncRNAs and DEmRNAs may play essential roles in rice innate immunity against RBSDV. Moreover, some of the lncRNA–mRNA regulatory relationships were experimentally verified in rice calli by a quick and effective method established in this study. Three DElncRNAs were selected to be tested, and the results indicated that five mRNAs were found to be regulated by them. Together, we give a whole landscape of rice mRNAs and lncRNAs in response to RBSDV infection, and a feasible method to rapidly verify the lncRNA–mRNA regulatory relationship in rice.