Reovirus, short for “respiratory enteric orphan virus,” is a widespread virus found in diverse environments. It can infect a broad range of hosts, including humans, animals, plants, protists, and fungi. Often not associated with overt disease, its presence in respiratory and gastrointestinal tracts led to its original designation as “orphan” viruses, meaning they were detected without a clear link to illness. However, ongoing research continues to uncover more about their interactions with various hosts.
Understanding Reovirus
Reoviruses belong to the family Reoviridae, a group of double-stranded RNA (dsRNA) viruses. Their structure is non-enveloped and they possess an icosahedral capsid, spheroidal, about 70 nanometers in diameter. The capsid is organized into two or three concentric protein layers surrounding a core that contains their segmented dsRNA genome. Their genome usually consists of 10 segments of dsRNA, encoding multiple proteins involved in virion structure and replication.
A notable member of the Reoviridae family is rotavirus, a related virus that causes distinctly different human health outcomes. Both are non-enveloped, double-stranded RNA viruses, but rotavirus is a leading cause of severe gastroenteritis, especially in children worldwide. In contrast, reovirus infections in humans are generally mild or asymptomatic. Rotaviruses have 11 genome segments, differing from the 10 segments found in orthoreoviruses.
Reovirus and Human Health
Human reovirus infections are common, yet often mild or subclinical, producing no noticeable symptoms. When symptoms occur, they can be varied, often involving the respiratory or gastrointestinal tracts. Common manifestations include mild fever, rhinitis, pharyngitis, or mild gastrointestinal upset with symptoms like diarrhea, nausea, and stomach pain. In rare instances, more severe conditions such as meningitis or encephalitis, involving the central nervous system, have been linked to reovirus serotypes 1 and 3.
Reovirus transmission occurs through fecal-oral contact or respiratory droplets. The virus can be detected in various bodily fluids and secretions, including feces, nasal or pharyngeal secretions, urine, blood, and cerebrospinal fluid. Due to the mild nature of most reovirus infections, specific antiviral treatments are not required. Management focuses on supportive care, addressing symptoms like fever with anti-fever medication, pain with analgesics, and dehydration with fluid intake.
Reovirus in Medical Research
Reovirus has garnered attention in medical research due to its oncolytic properties, meaning its ability to selectively target and destroy cancer cells. This therapeutic potential stems from the virus’s preference for replicating within cells that have activated Ras signaling pathways, a common characteristic in various types of cancer. When the Ras pathway is overactive, as often occurs in malignant cells, it creates an environment conducive to reovirus infection and replication.
Reovirus replication within cancer cells leads to their destruction through processes like apoptosis (programmed cell death) or autophagy (cellular self-digestion). Reovirus leaves healthy cells unharmed, making it a promising candidate for targeted cancer therapy. Beyond direct cell lysis, reovirus can also stimulate the immune system, enhancing the body’s natural defenses against tumors. Preclinical studies have shown its broad anticancer activity against various malignancies, including breast, colon, lung, and pancreatic cancers.
Clinical trials are currently exploring reovirus, often the unmodified type 3 Dearing strain (Pelareorep), both as a standalone therapy and in combination with conventional treatments like chemotherapy or radiotherapy, to improve patient outcomes. While direct injection into tumors is sometimes necessary, ongoing research aims to optimize its application in clinical settings.