Viral interference, also known as superinfection resistance,
[ is the inhibition of viral reproduction caused by previous exposure of cells to another virus. The exact mechanism for viral interference is unknown. Factors that have been implicated are the generation of ]interferon
Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten the ...
s by infected cells, and the occupation or down-modulation of cellular receptors.
__TOC__
Overview
Viral interference is considered the most common outcome of coinfection
Coinfection is the simultaneous infection of a host by multiple pathogen species. In virology, coinfection includes simultaneous infection of a single cell by two or more virus particles. An example is the coinfection of liver cells with hepatiti ...
, or the simultaneous infection of a host by two or more distinct viruses. The primary form of viral interference is known as superinfection
A superinfection is a second infection superimposed on an earlier one, especially by a different microbial agent of exogenous or endogenous origin, that is resistant to the treatment being used against the first infection. Examples of this in bact ...
exclusion, in which the initial infection stimulates a resistance to subsequent infection by related viruses. Interference can occur as well in the form of superinfection suppression, in which persistently infected cells hold off infection by unrelated viruses. Viral interference has also been observed to occur in the use of vaccines
A vaccine is a biological preparation that provides active acquired immunity
The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and pro ...
containing live-attenuated viruses, in both directions — in some cases vaccines disrupting viruses unrelated to those they were targeting, and in others wild viruses rendering vaccines of this kind less effective.
Examples
Bacteriophage T4
A primary infection by bacteriophage (phage) T4 of its '' E. coli'' host ordinarily leads to genetic exclusion of a secondarily infecting phage, preventing the secondary phage from contributing its genetic information to progeny. This viral interference depends on the expression by the primary phage of the gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s ''immunity'' (''imm'') and ''spackle'' (''sp''). The ''imm'' gp appears to enable the host exonuclease V to degrade the superinfecting phage DNA, and the ''sp'' gp appears to interfere with the DNA injection process of secondary phage.[ If the primary infecting phage is subjected to DNA damaging treatment prior to infection, this treatment tends to permit entry of the secondary phage's DNA, thus shifting reproduction from an asexual to a ]sexual
Sex is the biological distinction of an organism between male and female.
Sex or SEX may also refer to:
Biology and behaviour
*Animal sexual behaviour
**Copulation (zoology)
**Human sexual activity
**Non-penetrative sex, or sexual outercourse
** ...
mode and allowing rescue of the primary phage's genes.
Respiratory viruses
Interference has been observed to occur among endemic respiratory viruses. For example, human rhinovirus
The rhinovirus (from the grc, ῥίς, rhis "nose", , romanized: "of the nose", and the la, vīrus) is the most common viral infectious agent in humans and is the predominant cause of the common cold. Rhinovirus infection proliferates in tem ...
(HRV) infection has been shown to reduce the likelihood of codetection of other respiratory viruses, suggesting that it may confer a protective effect against other viruses such as influenza. The mechanism at play here has been suggested to be the expression of interferon-stimulated genes in the "target tissue" of HRV infection — the epithelium
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...
of the airway, where there has been observed to be an "unexpected high prevalence" of the virus, even among asymptomatic individuals. This process thus stimulates an antiviral state, shielding nearby cells from further infection. This potential interplay between viruses such as HRV and influenza may be one factor contributing to the timing and severity of their separate though overlapping "seasons".
Interference has been reported between respiratory viruses in non-human animals as well, such as between avian influenza viruses and Newcastle disease virus Newcastle usually refers to:
*Newcastle upon Tyne, a city and metropolitan borough in Tyne and Wear, England
*Newcastle-under-Lyme, a town in Staffordshire, England
*Newcastle, New South Wales, a metropolitan area in Australia, named after Newcastle ...
in chicken, turkeys, and ducks.
Live-attenuated vaccines
The first smallpox vaccine
The smallpox vaccine is the first vaccine to be developed against a contagious disease. In 1796, British physician Edward Jenner demonstrated that an infection with the relatively mild cowpox virus conferred immunity against the deadly smallpox ...
, developed by Edward Jenner
Edward Jenner, (17 May 1749 – 26 January 1823) was a British physician and scientist who pioneered the concept of vaccines, and created the smallpox vaccine, the world's first vaccine. The terms ''vaccine'' and ''vaccination'' are derived f ...
, used cowpox
Cowpox is an infectious disease caused by the ''cowpox virus'' (CPXV). It presents with large blisters in the skin, a fever and swollen glands, historically typically following contact with an infected cow, though in the last several decades more ...
to prevent smallpox
Smallpox was an infectious disease caused by variola virus (often called smallpox virus) which belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) c ...
infection. Indeed, the term "vaccinate" comes from the Latin phrase ''variolae vaccinae'', Jenner's name for cowpox.
Live enterovirus
''Enterovirus'' is a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine ('enteric' meaning intestinal).
Serologic ...
vaccines have been found to disrupt the spread of various unrelated respiratory viruses, such as influenza, HRV, and respiratory syncytial virus
Respiratory syncytial virus (RSV), also called human respiratory syncytial virus (hRSV) and human orthopneumovirus, is a common, contagious virus that causes infections of the respiratory tract. It is a negative-sense, single-stranded RNA virus. ...
(RSV), in addition to poliovirus (itself an enterovirus), a phenomenon attributed to viral interference. Similarly, during mass immunization campaigns against polio, vaccination seemed to confer some protection against unrelated enteroviruses as well. At the same time, enteroviruses were also found to interfere with the vaccines themselves, leading to instances of vaccine failure.
History
Viral interference was observed as early as the 16th century. However, it was not until the 20th century that it was described in detail, following experiments involving plants in 1929, animals in 1935, and bacteriophages in 1942.
2009 influenza pandemic
The emergence of a novel influenza A virus ( pandemic H1N1/09) in early 2009 afforded the opportunity to study how pandemic influenza and seasonal respiratory viruses might interact, placing the concept of viral interference "on more solid footing." The virus quickly spread across both the Northern and Southern Hemispheres through the middle of the year. While this is an unusual time for influenza activity in the north, the first wave of the pandemic
A pandemic () is an epidemic of an infectious disease that has spread across a large region, for instance multiple continents or worldwide, affecting a substantial number of individuals. A widespread endemic (epidemiology), endemic disease wi ...
in the south occurred during the typical influenza period. The pandemic virus quickly became the dominant strain of influenza, largely displacing the seasonal ones in many countries; however, complete replacement was not observed. Ultimately, activity generally peaked at the expected time for influenza in the Southern Hemisphere.
Despite the rapid spread around the world through the middle of the year, the pandemic remained in a lull during the summer in the north following an explosive outbreak in the spring. As predicted, the virus returned in epidemic proportions in the fall, earlier than the typical flu season but at a time when respiratory illnesses are known to become more prevalent. However, in countries such as Sweden, Norway, and France, the epidemic was "delayed" relative to its timing in other countries, such as the United States and Italy. This difference was attributed by some observers to a rhinovirus epidemic that broke out upon the reopening of schools, effectively "delaying" the rise in H1N1 cases until October. Studies on this potential interaction between HRV and the pandemic influenza at times came to divergent conclusions, however. While this "delay" in countries like Sweden was real (i.e., temporally speaking, the epidemic was later than in other places), studies also showed that coinfections were relatively common and that there was active cocirculation of the two viruses.
A systematic analysis of studies from 26 countries found that the influenza epidemic delayed the onset of RSV activity by an average of 0.58 months to 2.5 months. The effect was more pronounced in the Northern Hemisphere as compared to the Southern Hemisphere, perhaps due to the timing of the influenza outbreak relative to the period of typical RSV activity in each region; the tropics, meanwhile, experienced minimal delay. This impact persisted into the second RSV season after the start of the pandemic, albeit to a lesser degree, and was no longer observed by the third season.
COVID-19 pandemic
During the COVID-19 pandemic
The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identif ...
, the circulation of many respiratory viruses changed dramatically. Amid the rapid global spread of the pandemic SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...
throughout 2020, these viruses, including influenza, fell to historically low levels. Influenza activity remained virtually nonexistent into 2021, when it began to be detected more frequently, but was still low during the 2021–2022 flu season. RSV activity was similarly depressed during the first year of the pandemic, before resurging in 2021. By contrast, cases of HRV and respiratory enteroviruses declined at the onset of the pandemic but soon returned to prepandemic levels, circulating relatively normally.
The above reductions have generally been attributed to the imposition of nonpharmaceutical interventions, such as social distancing, mask use, and school closures. However, viral interference has also been suggested as the driving force, or least another driving force, behind this major decline in viral activity, based in part on the experience of the 2009 pandemic. For example, in the winter of 2021–2022, during the surge of the highly transmissible Omicron variant
Omicron (B.1.1.529) is a variant of SARS-CoV-2 first reported to the World Health Organization (WHO) by the Network for Genomics Surveillance in South Africa on 24 November 2021. It was first detected in Botswana and has spread to become the ...
of SARS-CoV-2 in the United States, influenza activity plummeted as the pandemic wave grew, peaking again in the spring once Omicron had subsided. A similar phenomenon was observed in Hong Kong in March 2022, when other respiratory viruses "disappeared" during the surge before returning in April. With respect to HRV and respiratory enteroviruses, whose behavior was evidently less affected during the pandemic, an apparent interplay between these and SARS-CoV-2, possibly mediated by viral interference, was identified in some places, such as California and South Korea. Although these viruses continued to circulate at near prepandemic levels, they were found to peak when SARS-CoV-2 activity was low and to decline as SARS-CoV-2 activity increased.
References
{{immunology-stub
Epidemiology
Virology