Virus internal labeling by inorganic nanoparticle is a suitable technique for single virus imaging. However, it is unknown that the effect of the internal inorganic nanoparticle on morphology and structure of viral core in mature enveloped Human immunodeficiency virus 1 (HIV-1). Also, the analysis of intact HIV-1 particles and virus-inorganic nanoparticle hybrids is almost impossible with conventional negative staining because HIV-1 is inherently fragile and unstable. Herein, we carried out morphological and structural analysis of a newly constructed quantum dot (QD)-encapsulated infectious HIV-1 particle by using an optimized procedure for the electron microscopic analysis of negatively stained HIV-1 particles. The virus fixation and staining conditions were optimized to ensure the integrity of HIV-1, allowing the ready access to structural information on the viral envelope and core. Morphological and structural analysis by optimized TEM provide key information about viruses, viral core and nanoparticles, which indicates that the encapsulation of quantum dots had no effect on the morphology or mean size of the viral particle, or on the shape, length, width, or angle of the HIV-1 core.