Abstract
Herpes simplex virus type 1 (HSV-1) has great potential to be applied as a viral tool for gene delivery or oncolysis. The broad infection tropism of HSV-1 makes it a suitable tool for targeting many different cell types, and its 150 kb double-stranded DNA genome provides great capacity for exogenous genes. Moreover, the features of neuron infection and neuron-to-neuron spread also offer special value to neuroscience. HSV-1 strain H129, with its predominant anterograde transneuronal transmission, represents one of the most promising anterograde neuronal circuit tracers to map output neuronal pathways. Decades of development have greatly expanded the H129-derived anterograde tracing toolbox, including polysynaptic and monosynaptic tracers with various fluorescent protein labeling. These tracers have been applied to neuroanatomical studies, and have contributed to revealing multiple important neuronal circuits. However, current H129-derived tracers retain intrinsic drawbacks that limit their broad application, such as yet-to-be improved labeling intensity, potential nonspecific retrograde labeling, and high toxicity. The biological complexity of HSV-1 and its insufficiently characterized virological properties have caused difficulties in its improvement and optimization as a viral tool. In this review, we focus on the current H129-derived viral tracers and highlight strategies in which future technological development can advance its use as a tool.
Highlights
Herpes simplex virus 1 (HSV-1) belongs to the α-subfamily of Herpesviridae, which is distinguished from the β- and γ-subfamilies by its fast reproduction and the ability to infect and establish latency in neurons [1]
In the associated virus (AAV)-assisted H129-dTK-tdT replication starter neurons, severe damage is observed within 3–7 days, and starter neurons co-infected by H129-dTK and AAV-thymidine kinases (TK) cannot be detected at 10 days (Figure 2I) [18]
Eliminating/reducing nonspecific retrograde transmission and increasing anterograde transmission efficiency are some of the key tasks for future H129 tracer development, which requires a better understanding of the underlying mechanisms
Summary
Herpes simplex virus 1 (HSV-1) belongs to the α-subfamily of Herpesviridae, which is distinguished from the β- and γ-subfamilies by its fast reproduction and the ability to infect and establish latency in neurons [1]. HSV-1 occasionally causes severe or even life-threatening diseases such as retinitis, keratitis [5], encephalitis [6], and systemic infection [7]. These lead to higher morbidity and mortality rates, especially in vulnerable neonates and immunosuppressed individuals [8]. Growing evidence supports the direct relationship between HSV-1 infection and Alzheimer’s disease [9,10], highlighting the important influence of this neurotropic virus on the nervous system. The reactivated virus may invade the central nervous system by infecting further neuronal cells causing encephalitis.
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