Understanding the antibody response to SARS-CoV-2, the virus responsible for COVID-19, is crucial to comprehending disease progression and the significance of vaccine and therapeutic development. The emergence of highly contagious variants poses a significant challenge to humoral immunity, underscoring the necessity of grasping the intricacies of specific antibodies. This review emphasizes the pivotal role of antibodies in shaping immune responses and their implications for diagnosing, preventing, and treating SARS-CoV-2 infection. It delves into the kinetics and characteristics of the antibody response to SARS-CoV-2 and explores current antibody-based diagnostics, discussing their strengths, clinical utility, and limitations. Furthermore, we underscore the therapeutic potential of SARS-CoV-2-specific antibodies, discussing various antibody-based therapies such as monoclonal antibodies, polyclonal antibodies, anti-cytokines, convalescent plasma, and hyperimmunoglobulin-based therapies. Moreover, we offer insights into antibody responses to SARS-CoV-2 vaccines, emphasizing the significance of neutralizing antibodies in order to confer immunity to SARS-CoV-2, along with emerging variants of concern (VOCs) and circulating Omicron subvariants. We also highlight challenges in the field, such as the risks of antibody-dependent enhancement (ADE) for SARS-CoV-2 antibodies, and shed light on the challenges associated with the original antigenic sin (OAS) effect and long COVID. Overall, this review intends to provide valuable insights, which are crucial to advancing sensitive diagnostic tools, identifying efficient antibody-based therapeutics, and developing effective vaccines to combat the evolving threat of SARS-CoV-2 variants on a global scale.

To maintain growth and to successfully reproduce, organisms must protect key functions in specific tissues, particularly when countering pathogen invasion using internal defensive proteins that may disrupt their own developmental processes. The rice immune receptor XA21 confers race-specific resistance against Xanthomonas oryzae pv. oryzae , which causes the deadly disease bacterial leaf blight. Here, we demonstrate that XA21 is cleaved by the rhomboid-like protease OsRBL3b, likely within its transmembrane domain. OsRBL3b mRNA transcripts are preferentially expressed in rice spikelets. Rice plants expressing Xa21 but lacking a functional OsRBL3b displayed impaired anther dehiscence and pollen viability, resulting in male sterility and yield reduction with high levels of XA21 protein present in spikelets during anthesis. In leaves, osrbl3b mutants expressing XA21 had normal levels of this resistance protein and disease immunity. This balance between reproduction and disease resistance through the specific expression of a rhomboid protease may be key to limiting the detrimental effects of an active immune response and may be useful in future for genetic improvement of crops.

Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic gammaherpesvirus that is the causative agent of primary effusion lymphoma and Kaposi’s sarcoma. In healthy carriers, KSHV remains latent, but a compromised immune system can lead to lytic viral replication that increases the probability of tumorigenesis. RIG-I-like receptors (RLRs) are members of the DExD/H box helicase family of RNA binding proteins that recognize KSHV to stimulate the immune system and prevent reactivation from latency. To determine if other DExD/H box helicases can affect KSHV lytic reactivation, we performed a knock-down screen that revealed DHX29-dependent activities appear to support viral replication but, in contrast, DDX24 and DDX49 have antiviral activity. When DDX24 or DDX49 are overexpressed in BCBL-1 cells, transcription of all lytic viral genes and genome replication were significantly reduced. RNA immunoprecipitation of tagged DDX24 and DDX49 followed by next-generation sequencing revealed that the helicases bind to mostly immediate-early and early KSHV mRNAs. Transfection of expression plasmids of candidate KSHV transcripts, identified from RNA pull-down, demonstrated that KSHV mRNAs stimulate type I interferon (alpha/beta) production and affect the expression of multiple interferon-stimulated genes. Our findings reveal that host DExD/H box helicases DDX24 and DDX49 recognize gammaherpesvirus transcripts and convey an antiviral effect in the context of lytic reactivation.

Kaposi sarcoma‐associated herpesvirus (KSHV), a gamma‐herpesvirus, is the main etiological agent of several tumors, including Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). The large, double‐stranded viral genome of KSHV is maintained as a latent episome in the nucleus of host cells, where a small subset of viral genes is expressed that facilitate evasion of immune responses and promotion of cell survival and proliferation supporting tumorigenesis. The major latency‐associated nuclear antigen (LANA) is an essential viral factor that is required for genome replication and segregation to maintain viral genomes within dividing cells. Given the essential role of LANA to maintain viral latency, efforts have focused on targeting LANA's role in replication and segregation as a mechanism to overcome latency and tumorigenesis. However, given the complexity in small molecule targeting to DNA‐binding domains, current efforts focused on drugging LANA continue to reach potency milestones for clinical trials. Here, we developed a HaloTag‐based PROTAC model as a proof‐of‐concept for targeted LANA protein degradation. Our findings highlight the power of a PROTAC‐based strategy on eliminating LANA and viral persistence in tissue culture demonstrating promise in the on‐going challenge for targeting this major viral factor in KSHV latency.

Comparative transcriptome analyses of gamma herpesviruses have been revolutionized by long‐read sequencing and integrative multi‐omics approaches, enabling unprecedented resolution of viral gene expression. Cross‐species studies of Kaposi's sarcoma‐associated herpesvirus (KSHV), Epstein–Barr virus (EBV), and murine gamma herpesvirus 68 (MHV68) have uncovered a vast diversity of transcript isoforms, including alternative 5′/3′ UTR variants, alternative splice isoforms, and transcripts encoding truncated or extended coding sequences. These efforts revealed novel transcript isoforms harboring partial open reading frames, entirely new ORFs, and an expanding repertoire of viral non‐coding RNAs. Additional regulatory mechanisms, such as promoter dependence on viral replication factors, selective polyadenylation site usage, frameshifting via alternative splicing, and extensive readthrough transcription, further illustrate the complex strategies governing gamma herpesvirus transcriptomes. This review synthesizes these discoveries, highlighting transcriptional strategies employed by gamma herpesviruses for persistence through different phases of replication, while outlining how integrative transcriptomics has reshaped our understanding of herpesvirus gene regulation.