Inactivated HSV Type 1 Stock

The rhizome of Dryopteris crassirhizoma Nakai is an important traditional Chinese medicine listed in Chinese Pharmacopoeia for the treatment of parasitic infestation and viral diseases. In this work, ten enantiomeric pairs of new acylphloroglucinol meroterpenoids, ( +/- )-dryocrassoids A - J [( +/- )-1 - 101, along with six known acylphloroglucinols (11-16) were isolated from the rhizomes of D. crassirhizoma. Notably, these new enantiomers were the first examples of meroterpenoids constructed by acylphloroglucinols and nerolidol-type sesquiterpenes, while ( +/- )-1a/1b, ( +/- )-2a/2b, ( +/- )-4a/4b were obtained as the inseparable interconverting mixtures of keto and enol tautomers. The new structures and absolute configurations were identified by the interpretation of high resolution electron spray ionization mass spectrum (HRESIMS), nuclear magnetic resonance (NMR) spectroscopic data, and quantum chemical electronic circular dichroism (ECD) calculations. In addition, these compounds were assayed for the in vitro antiviral activities against herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and respiratory syncytial virus (RSV). The results indicated that most of the compounds showed anti-HSV-1 and anti-RSV effects to different extent under the concentration of 100 mu M. This study provided evidences for further study and utilization of D. crassirhizoma in medicinal products.

Herpes simplex virus 1 (HSV-1) can induce damage in brain regions that in-clude the hippocampus and associated limbic structures. These neurogenic niches are important because they are associated with memory formation and are highly enriched with neural progenitor cells (NPCs). The susceptibility and fate of HSV-1-infected NPCs are largely unexplored. We differentiated human induced pluripotent stem cells (hiPSCs) into NPCs to generate two-dimensional (2D) and three-dimensional (3D) culture models to examine the interaction of HSV-1 with NPCs. Here, we show that (i) NPCs can be effi-ciently infected by HSV-1, but infection does not result in cell death of most NPCs, even at high multiplicities of infection (MOIs); (ii) limited HSV-1 replication and gene expres-sion can be detected in the infected NPCs; (iii) a viral silencing mechanism is established in NPCs exposed to the antivirals (E)-5-(2-bromovinyl)-2=-deoxyuridine (5BVdU) and alpha interferon (IFN-a) and when the antivirals are removed, spontaneous reactivation can oc-cur at low frequency; (iv) HSV-1 impairs the ability of NPCs to migrate in a dose-dependent fashion in the presence of 5BVdU plus IFN-a; and (v) 3D cultures of NPCs are less susceptible to HSV-1 infection than 2D cultures. These results suggest that NPC pools could be sites of HSV-1 reactivation in the central nervous system (CNS). Finally, our results highlight the potential value of hiPSC-derived 3D cultures to model HSV-1-NPC interaction. IMPORTANCE This study employed human induced pluripotent stem cells (hiPSCs) to model the interaction of HSV-1 with NPCs, which reside in the neurogenic niches of the CNS and play a fundamental role in adult neurogenesis. Herein, we provide evidence that in NPCs infected at an MOI as low as 0.001, HSV-1 can establish a latent state, sug-gesting that (i) a variant of classical HSV-1 latency can be established during earlier stages of neuronal differentiation and (ii) neurogenic niches in the brain may constitute additional sites of viral reactivation. Lytic HSV-1 infections impaired NPC migration, which represents a critical step in neurogenesis. A difference in susceptibility to HSV-1 infection between two-dimensional (2D) and three-dimensional (3D) NPC cultures was observed, highlighting the potential value of 3D cultures for modeling host-pathogen in-teractions. Together, our results are relevant in light of observations relating HSV-1 infec-tion to postencephalitic cognitive dysfunction.