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The COVID-19 global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has infected hundreds of millions of individuals. Following COVID-19 infection, a subset can develop a wide range of chronic symptoms affecting diverse organ systems referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. A National Institutes of Health-sponsored initiative, RECOVER: Researching COVID to Enhance Recovery, has sought to understand the basis of long COVID in a large cohort. Given the range of symptoms that occur in long COVID, the mechanisms that may underlie these diverse symptoms may also be diverse. In this review, we focus on the emerging literature supporting the role(s) that viral persistence or reactivation of viruses may play in PASC. Persistence of SARS-CoV-2 RNA or antigens is reported in some organs, yet the mechanism by which they do so and how they may be associated with pathogenic immune responses is unclear. Understanding the mechanisms of persistence of RNA, antigen or other reactivated viruses and how they may relate to specific inflammatory responses that drive symptoms of PASC may provide a rationale for treatment.

While many studies have assessed immune responses to SARS-CoV-2 infection, none have studied functional antibody responses before and after vaccination of exposed patients in New Mexico in the United States. Here, we evaluate antibody binding, antibody neutralization, and antibody dependent cell-mediated cytotoxicity (ADCC) responses from convalescent patients between September 2020 and April 2021. Our results indicate that binding, neutralizing, and ADCC titers remained durable over an estimated 4-month period or were boosted by vaccination. Antibody binding titer stability was comparable to that of antibodies against four common viruses. Hispanic and Latino responses were similar to non-Hispanic/Latino responses in this cohort. Overall, these data shed light on functional antibody responses to SARS-CoV-2 in pre-alpha variant waves in New Mexico.

Alphaviruses are important human and animal pathogens that can cause a range of debilitating symptoms and are found worldwide. These include arthralgic diseases caused by Old-World viruses and encephalitis induced by infection with New-World alphaviruses. Non-coding RNAs do not encode for proteins, but can modulate cellular response pathways in a myriad of ways. There are several classes of non-coding RNAs, some more well-studied than others. Much research has focused on the mRNA response to infection against alphaviruses, but analysis of non-coding RNA responses has been more limited until recently. This review covers what is known regarding host cell non-coding RNA responses in alphavirus infections and highlights gaps in the knowledge that future research should address.

Orthohantaviruses are diverse zoonotic RNA viruses. Small mammals, such as mice and rats are common chronic, asymptomatic hosts that transmit the virus through their feces and urine. In North America, hantavirus infection primarily causes hantavirus cardiopulmonary syndrome (HCPS), which has a mortality rate of nearly 36%. In the United States of America, New Mexico (NM) is leading the nation in the number of HCPS-reported cases (N = 129). However, no reported cases of HCPS have occurred within eastern NM. In this study, we assessed the prevalence of Sin Nombre virus (SNV) in rodent assemblages across eastern NM, using RT-qPCR. We screened for potential rodent hosts in the region, as well as identified areas that may pose significant infection risk to humans. We captured and collected blood and lung tissues from 738 rodents belonging to 23 species. 167 individuals from 16 different species were positive for SNV RNA by RT-qPCR, including 6 species unreported in the literature: Onychomys leucogaster (Northern grasshopper mouse), Dipodomys merriami (Merriam’s kangaroo rat), Dipodomys ordii (Ord’s kangaroo rat), Dipodomys spectabilis (Banner-tailed kangaroo rat), Perognathus flavus (Silky pocket mouse), and Chaetodipus hispidus (Hispid pocket mouse). The infection rates did not differ between sexes or rodent families (i.e., Cricetidae vs. Heteromyidae). Generalized linear model showed that disturbed habitat types positively influenced the prevalence of SNV at sites of survey. Overall, the results of this study indicate that many rodent species in east New Mexico have the potential to maintain SNV in the environment, but further research is needed to assess species specific infectivity mechanisms and potential risk to humans.

Ebola Zaire virus is highly pathogenic for humans, with case fatality rates approaching 90% in large outbreaks in Africa. The virus replicates in macrophages and dendritic cells (DCs), suppressing production of type I interferons (IFNs) while inducing the release of large quantities of proinflammatory cytokines. Although the viral VP35 protein has been shown to inhibit IFN responses, the mechanism by which it blocks IFN production has not been fully elucidated. We expressed VP35 from a mouse-adapted variant of Ebola Zaire virus in murine DCs by retroviral gene transfer, and tested for IFN transcription upon Newcastle Disease virus (NDV) infection and toll-like receptor signaling. We found that VP35 inhibited IFN transcription in DCs following these stimuli by disabling the activity of IRF7, a transcription factor required for IFN transcription. By yeast two-hybrid screens and coimmunoprecipitation assays, we found that VP35 interacted with IRF7, Ubc9 and PIAS1. The latter two are the host SUMO E2 enzyme and E3 ligase, respectively. VP35, while not itself a SUMO ligase, increased PIAS1-mediated SUMOylation of IRF7, and repressed Ifn transcription. In contrast, VP35 did not interfere with the activation of NF-kappaB, which is required for induction of many proinflammatory cytokines. Our findings indicate that Ebola Zaire virus exploits the cellular SUMOylation machinery for its advantage and help to explain how the virus overcomes host innate defenses, causing rapidly overwhelming infection to produce a syndrome resembling fulminant septic shock.

Zika virus (ZIKV) is an emerging pathogen with no approved therapeutics and only limited diagnostics available. To address this gap, six mouse single-chain antibodies (scFvs) to ZIKV envelope (E) protein were isolated rapidly and efficiently from a ribosome-displayed antibody library constructed from the spleens of five immunized mice. In this report, we have generated a panel of mouse scFvs to ZIKV E protein using ribosome display. The six scFvs demonstrated no cross-reactivity with DENV2 NGC envelope protein, suggesting specificity for ZIKV E protein. These scFvs showed differences in their affinity: two (scFv45-3, scFv63-1) of them were dominant after four rounds of panning, and showed higher affinity (an apparent Kd values from 19 to 27 nM) than the other four (scFv5-1, scFv7-2, scFv38-1, and scFv51-2). All six scFvs showed ZIKV-neutralizing activity in the plaque reduction neutralization test (PRNT) assay and their neutralizing activity was positively correlated with their affinities. The scFvs (45-3 and 63-1) with highest affinity may have dual utility as diagnostics capable of recognizing ZIKV E subtypes and may be further developed to treat ZIKV infection. Our approach has the added advantage of generating Fc receptor-deficient antibodies, minimizing concern of antibody-dependent enhancement (ADE) of infection.

Orthohantaviruses are negative-sense RNA viruses that can cause hantavirus cardiopulmonary syndrome (HCPS) in humans. In the United States, Sin Nombre orthohantavirus (SNV) is the primary cause of HCPS, with a fatality rate of 36% and most cases occuring in the southwestern states. The western deer mouse, Peromyscus sonoriensis, is the primary reservoir for SNV; however, it remains unclear if alternative reservoirs exist. We conducted an extensive survey of SNV genetic prevalence in wild-caught small mammal communities throughout New Mexico and observed that 27% of all animals were positive for SNV. Through longitudinal trapping at a site of patient exposure, we found that SNV circulates at a high rate in multiple species over time. Furthermore, we isolated live SNV from tissues and feces from multiple small mammal species, demonstrating infectious virus in alternative and novel reservoirs. Altogether, this work shows that SNV is widely prevalent and persistent throughout New Mexico in multiple small mammal reservoirs that can harbor and shed infectious virus. This encourages future work for additional surviellance efforts and revaluates host-species dynamics for New World hantaviruses.

Virus-like particles from a variety of RNA bacteriophages have turned out to be useful platforms for delivery of vaccine antigens in a highly immunogenic format. Here we update the current state of development of RNA phage VLPs as platforms for presentation of diverse antigens by genetic, enzymatic, and chemical display methods.

The microbiome remains a top area of research, and it is now common to examine any organic and inorganic samples for bacterial colonization. However, due to the ubiquity of bacteria in the environment, separating the low-burden colonization of bacteria from the possible contamination of laboratory reagents remains problematic. When examining samples of expected low bacterial burden, it is common to first amplify any bacterial DNA present through PCR before sequencing. In this work, we examined nine different commercial PCR enzymes and their reaction components as possible sources of bacterial DNA contamination. We found contaminating bacterial DNA in seven of the nine reactions, and this DNA was shown to come from a variety of species. Importantly, we were able to perform these studies solely with endpoint PCR and Sanger sequencing, which are more accessible and affordable than high-throughput, short-read sequencing and real-time PCR. This work confirms that there needs to be an increased emphasis on including control reactions in microbiome studies so that contaminating DNA sequences can be identified and addressed, and that this can be achieved with minimal resources.

The SARS-CoV-2 pandemic has highlighted the need for protective and effective personal protective equipment (PPE). Research has shown that SARS-CoV-2 can survive on personal protective equipment, such as commonly used surgical masks. Methods are needed to inactivate virus on contaminated material. We show here that embedding viral-disinfecting compounds during the manufacturing of surgical masks inactivates a high dose (up to 1 × 105 pfu) of live, authentic SARS-CoV-2 within minutes.