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Human alpha herpesviruses herpes simplex virus (HSV-1) and varicella zoster virus (VZV) establish latency in various cranial nerve ganglia and often reactivate in response to stress-associated immune system dysregulation. Reactivation of Epstein Barr virus (EBV), VZV, HSV-1, and cytomegalovirus (CMV) is typically asymptomatic during spaceflight, though live/infectious virus has been recovered and the shedding rate increases with mission duration. The risk of clinical disease, therefore, may increase for astronauts assigned to extended missions (>180 days). Here, we report, for the first time, a case of HSV-1 skin rash (dermatitis) occurring during long-duration spaceflight. The astronaut reported persistent dermatitis during flight, which was treated onboard with oral antihistamines and topical/oral steroids. No HSV-1 DNA was detected in 6-month pre-mission saliva samples, but on flight day 82, a saliva and rash swab both yielded 4.8 copies/ng DNA and 5.3 × 104 copies/ng DNA, respectively. Post-mission saliva samples continued to have a high infectious HSV-1 load (1.67 × 107 copies/ng DNA). HSV-1 from both rash and saliva samples had 99.9% genotype homology. Additional physiological monitoring, including stress biomarkers (cortisol, dehydroepiandrosterone (DHEA), and salivary amylase), immune markers (adaptive regulatory and inflammatory plasma cytokines), and biochemical profile markers, including vitamin/mineral status and bone metabolism, are also presented for this case. These data highlight an atypical presentation of HSV-1 during spaceflight and underscore the importance of viral screening during clinical evaluations of in-flight dermatitis to determine viral etiology and guide treatment. [ABSTRACT FROM AUTHOR]

Infants of HIV positive mothers can acquire HIV infection by various routes, but even in the absence of antiviral treatment, the majority of these infants do not become infected. There is evidence that maternal antibodies may provide some protection from infection, but gestational maternal antibodies have not yet been characterized in detail. One of the most studied vertically-infected infants is BG505, as the virus from this infant yielded an Envelope protein that was successfully developed as a stable trimer. Here, we isolated and characterized 39 HIV specific neutralizing monoclonal antibodies (nAbs) from MG505, the mother of BG505, at a time point just prior to vertical transmission. These nAbs belonged to 21 clonal families, employed a variety of VH genes, many were specific for the HIV-1 Env V3 loop, and this V3 specificity correlated with measurable antibody-dependent cellular cytotoxicity (ADCC) activity. The isolated nAbs did not recapitulate the full breadth of heterologous nor autologous virus neutralization by contemporaneous plasma. Notably, we found that the V3-targeting nAb families neutralized one particular maternal Env variant even though all tested variants had low V3 sequence diversity and were measurably bound by these nAbs. None of the nAbs neutralized BG505 transmitted virus. Furthermore, the MG505 nAb families were found at relatively low frequencies within the maternal B cell repertoire: all less than 0.25% of total IgG sequences. Our findings illustrate an example of the diversity of HIV-1 nAbs within one mother, cumulatively resulting in a collection of antibody specificities that can contribute to the transmission bottleneck. [ABSTRACT FROM AUTHOR]

To date more than 400 genomes of herpes simplex virus 1 (HSV-1) and the distantly related HSV-2 have been examined using deep sequencing techniques. This powerful approach has been especially useful for revealing the global genetic diversity that exists within and between strains of each virus species. However, most early methods for high-throughput sequencing required the input of abundant viral genomic DNA to enable the successful production of sequencing libraries, and the generation of sufficient short-read sequencing data for de novo genome assembly and similar applications. Therefore, the majority of sequenced HSV strains have been cultured and expanded in vitro prior to genomic analysis, to facilitate isolation of sufficient viral DNA for sequencing-library preparation. Here, we describe an in-solution targeted enrichment procedure for isolating, enriching, and sequencing HSV genomic DNA directly from clinical specimens. When this enrichment technique is combined with traditional sequencing-library preparation procedures, the need for in vitro culturing, expansion, and purification of viral DNA is eliminated. Furthermore, enrichment reduces the large amount of nonviral DNA that is typically present in specimens obtained directly from natural infections, thereby increasing the likelihood of successful viral genome sequencing and assembly. We have used this approach to prepare viral DNA libraries from clinical specimens derived from skin swabs, saliva, blood, and similar sources. We then use these libraries for deep sequencing and successful de novo assembly of the ~152 kb viral genomes, at coverage depths exceeding 100-1000×, for both HSV-1 and HSV-2.

Here we present a personalized viral genomics approach to investigating a rare case of perinatal herpes simplex virus 1 (HSV-1) transmission that ended in death of both mother and neonate. We sought to determine whether the virus involved in this rare case had any unusual features that may have contributed to the dire patient outcome. A pregnant woman with negative HerpeSelect antibody test underwent cesarean section at 30 wk gestation and died the same day. The premature newborn died 5 d later. Both individuals were found postmortem to have positive blood HSV-1 PCR tests. Using oligonucleotide enrichment and deep sequencing, we determined that viral transmission from mother to infant was nearly perfect at the consensus genome level. At the virus population level, 77% of minor variants (MVs) in the mother's blood also appeared on the neonate's skin, of which more than half were disseminated into the neonate's blood. We also detected nonmaternal MVs that arose de novo in the neonate's viral populations. Of note, one de novo MV in the neonate's skin virus induced a nonsynonymous mutation in the UL6 protein, which is a component of the portal that allows DNA entry into new progeny capsids. This case suggests that perinatal viremic HSV-1 transmission includes the majority of genetic diversity from the maternal virus population and that new, nonsynonymous mutations can occur after relatively few rounds of replication. This report expands our understanding of viral transmission in humans and may lead to improved diagnostic strategies for neonatal HSV-1 acquisition., (© 2019 Shipley et al.; Published by Cold Spring Harbor Laboratory Press.)