Some science behind the scenes

Virus latency

Virus latency (or viral latency) is the ability of a pathogenic virus to lie dormant (latent) within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection. Latency is the phase in certain viruses' life cycles in which, after initial infection, proliferation of virus particles ceases. However, the viral genome is not fully eradicated. The result of this is that the virus can reactivate and begin producing large amounts of viral progeny without the host being infected by new outside virus, denoted as the lytic part of the viral life cycle, and stays within the host indefinitely.

Virus latency is not to be confused with clinical latency during the incubation period when a virus is not dormant.

Examples

An example of a family of viruses able to do this is the Herpes Virus family, Herpesviridae, all of which establish latent infection. Herpes virus includes Chicken-pox virus and Herpes simplex viruses (HSV-1, HSV-2).  The Gammaherpesvirinae subfamily establishes itself in cells of the immune system, such as B-cells in the case of Epstein-Barr Virus.  In the case of varicella zoster virus, after an initial acute infection (chickenpox) the virus lies dormant until reactivated as herpes zoster.  Persistent infection by the human papilloma virus may lead to cervical cancer as a result of cellular transformation. Cytomegalovirus [CMV] is able to establish latent infection, as is the Rubella virus.

The BK virus - many people who are infected with this virus are asymptomatic. If primary [first infection] symptoms appear, they tend to be mild: respiratory infection or fever. The virus then disseminates to the kidneys and urinary tract where it persists for the life of the individual. It is thought that up to 80% of the population contains a latent form of this virus.

Although the research seems a little unclear, there appears to be a latency like capability [it may not be latency it may be multiplicity reactivation] in the mumps virus

In recent years, large mumps outbreaks, involving mainly adolescents and young adults, have re-emerged in several countries. We investigated a large mumps outbreak, evaluated the association between mumps clinical severity (complications, hospitalization) and vaccination status (number of previous measles, mumps and rubella - MMR vaccine doses), and assessed vaccine effectiveness. The first mumps cases emerged in an ultra-orthodox boys' school in Jerusalem and were epidemiologically linked to the mumps outbreak in New York. Overall, 3130 mumps cases were notified in the Jerusalem district during September 2009-August 2011 (median age 13y, 64% males). …………….. The outbreak was characterized by predominance of male students; the majority of whom had been previously vaccinated.   PMID:  25874726

The following paper was written in 1975 and it is clear that much of what was known then has been forgotten.  Part of the problem appears to be that they called them 'slow viruses'

There is evidence for persisting infection in congenital rubella and the herpes group of viruses including cytomegalovirus infections. Hepatitis types A and B are candidates for inclusion in the category of persisting viral infections. The rubeola or measles virus is established as a persistent virus which causes elevated antibodies in the serum and cerebrospinal fluid of many patients with severe demyelinating disease such as subacute sclerosing panencephalitis and multiple sclerosis. Elevated antibodies against vaccinia virus have been found in the cerebrospinal fluid of some patients with multiple sclerosis and neuromyelitis optica, a rare form of multiple sclerosis. PMID: 165638

The Simian 40 virus is a latent virus.

HIV is a virus with latency..................

 HIV latency is the chief obstacle to eradicating HIV … findings of latency being "hardwired" into HIV's gene-regulatory circuitry appear inconsistent with latency being an evolutionary accident, given HIV's rapid mutation rate. Here, we propose that latency is an evolutionary "bet-hedging" strategy whose frequency has been optimized to maximize lentiviral transmission by reducing viral extinction during mucosal infections. PMID:  25723173

Provirus

A provirus is a virus genome that is integrated into the DNA of a host cell.

These viruses are extremely dangerous, as automatic host cell division results in replication of the virus's genes, and it is nearly impossible to remove an integrated provirus from an infected cell without killing the cell.  Viruses that integrate into the host cell's genome stay there as long as the cell lives.

One of the best-studied viruses that does this is HIV. HIV uses reverse transcriptase to create a DNA copy of its RNA genome. HIV latency allows the virus to largely avoid the immune system. Like other viruses that go latent, it does not typically cause symptoms while latent. Unfortunately, HIV in proviral latency is nearly impossible to target with antiretroviral drugs.

Retroviruses

A certain type of latency could be ascribed to the endogenous retroviruses. These viruses have incorporated into the human genome in the distant past, and are now passed through reproduction. Generally these types of viruses have become highly evolved, and have lost the expression of many gene products. Some of the proteins expressed by these viruses have co-evolved with host cells to play important roles in normal processes.

Implications

Viruses that can cause latent infection can also cause cancer.  The latent infection can transform the cell, and force the cell into uncontrolled cell division. This is a result of the random insertion of the viral genome into the hosts own gene and expression of host cellular growth factors for the benefit of the virus. A famous event of this actually happening with gene therapy through the use of retroviral vectors is the Necker Hospital in Paris, where 20 young boys received treatment for a genetic disorder, after which 5 developed leukemia-like syndromes.

There are also very serious implications for vaccines.  If a person is vaccinated with any live virus able to exhibit virus latency, one has to all intents and purposes given them disease not prevented disease, a disease like cancer which only emerges later in life.  For example

The live attenuated Oka varicella vaccine (vOka), derived from clade 2 wild-type (wt) virus pOka, is used for routine childhood immunization in several countries, including the United States,......... vOka can cause varicella, establish latency, and reactivate to cause herpes zoster (HZ).  We also evaluated the 4 vOka markers in an isolate obtained from a case of vaccine-caused HZ.  PMID: 22378912

 and

Multiple sclerosis is a chronic inflammatory, autoimmune, demyelinating, disease but also degeneration of axons, with mainly progressive course, causing greater or lesser degree of disability. In addition to genetic predisposition the environmental factors, with particular importance of early viral infection, have an essential role in the development of MS. These are called long-acting viruses that remain hidden in the body for years by encouraging latent immunological changes in the body, eventually resulting in autoimmune demyelination and the appearance of disease symptoms, which confirms the high titer of antibodies to certain viruses in patients with the MS. To first of all herpes simplex virus, Epstein Barr virus, cytomegalovirus and rubella virus.

PMID: 22937690

 Immunity to a virus which has become latent is only achieved for a short space of time.  Over time loss of the antibodies occurs over time and thus the virus can simply reappear in its new virulent form

The present article illustrates the extent of secondary vaccine failure after vaccination for measles, mumps and rubella (MMR). Secondary vaccine failure means loss of the immunity induced by vaccination to such an extent that infection becomes possible. Serological investigations carried out with follow-up periods of up to 16 years after vaccination for measles, 21 years after vaccination for rubella and 12 years after vaccination for mumps reveal that loss of antibodies occurs with the elapse of time but that the clinical significance of this is probably very limited. Where all three types of vaccination are concerned, secondary vaccine failure has hitherto been very seldom. Infection with measles after secondary vaccine failure is generally described as running a milder course. In rare cases, rubella re-infection has resulted in infection in utero, so that a slight risk of congenital rubella cannot be entirely excluded after successful vaccination. No extensive systematic investigations of the effect of revaccination have been carried out and, similarly, the optimal interval between two or more vaccinations has not been illustrated in more detail in the literature. Subclinical infection is not uncommon after all three vaccines. Where measles is concerned, immunity may possibly be regarded as a continuum which, depending upon the antibody level, protects the individual from various degrees of clinical disease. If wild virus can be spread via individuals with subclinical infections, it is doubtful whether population immunity (herd immunity), which is necessary to eliminate the three diseases, can be attained in large populations.

PMID: 1509566

 

 

Observations

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