Perspective on Adenoviruses: Epidemiology, Pathogenicity, and Gene Therapy

Abstract

Human adenoviruses are large (150 MDa) doubled-stranded DNA viruses that cause respiratory infections. These viruses are particularly pathogenic in healthy and immune-compromised individuals, and currently, no adenovirus vaccine is available for the general public. The purpose of this review is to describe (i) the epidemiology and pathogenicity of human adenoviruses, (ii) the biological role of adenovirus vectors in gene therapy applications, and (iii) the potential role of exosomes in adenoviral infections.

Keywords: Mastadenovirus; adenovirus; epidemiology; exosomes; gene therapy; serotype.

Figure 1

A digital cryo-electron micrograph of the Adenovirus serotype 5 (Ad-5)/HVR5-33RGD vector. Adenoviruses are non-enveloped, double-stranded DNA viruses that cause cold-like infections of the upper respiratory tract. These viruses have an icosahedral-shaped capsid that ranges from 90–100 nm in diameter and a ~36-kb genome. This image was collected on a Tecnai-12 microscope using a Gatan UltraScan 1000 (2k × 2k) CCD camera. The scale bar represents 1,000 Å. Image provided courtesy of Dr. Phoebe Stewart, Case Western Reserve University, Cleveland, OH, USA.

Figure 2

Mechanisms of HAdV spread within the body. HAdV may be transmitted directly or indirectly. These viruses can adversely impact body systems and cause organ dysfunction. HAdV can evade the immune response and produce persistent or latent infections. The organs are represented in purple, while the body systems are represented in blue. The biological status of the infected host is indicated in green.

Figure 3

Exosomes mediate HAdV attachment and entry. The coxsackie and adenovirus receptor (CAR) mediates the entry of HAdv into human cells. Exosomes act as carriers for viruses, and this inclusion is important for viral survival, spread, and infection in the host organism. The HAdV binds to exosomes, enters cells via phosphatidylserine/TIM-4 interactions or other binding proteins. In addition, the virus injects their DNA into the host cell, which produces copies of its genes and proteins, resulting in transmission. Multivesicular bodies (MVBs).