Replicative form infectivity

Canine parvovirus, first identified in 1978, is now endemic.455,456 Childhood fifth disease is also caused by a parvovirus.456,457 When these single-stranded DNA viruses infect cells a double-stranded replicative form of DNA arises by synthesis of the complementary negative strand alongside the original positive DNA strand. Many copies of the replicative form are then synthesized. The negative strands of the replicative forms serve as templates for synthesis of numerous new positive strands that are incorporated into the progeny viruses. The whole process may take only 20 minutes. Some parvoviruses are unable to reproduce unless the cell is also infected by a larger adenovirus. 

Hirota, K Sherker, A. H., Omata, M., Yokosuka, O., and Okuda, K. (1987) Effects of adenine arabinoside on scrum and intraheparic replicative forms of duck hepatitis B virus in chronic infection. Hepatology 7, 24-28. 

It has been reported that a ribonuclease is induced when extracts of interferon-treated non-infected cell extracts are incubated with dsRNA and ATP (2j). Since dsRNA is present in interferon-treated mengo virus-infected cells the induction of a dsRNA dependent ribonuclease might occur. Kinetic assays for ribonuclease activity showed a marked increase in ribonuclease activity of the P-20 from interf eron-treatment, mengo virus-infected cells. Poly C, Poly U and poly A were also degraded by the enzyme, whereas (5h) replicative form of mengo virus was not degraded. Extracts from interferon-treated non-infected cells did not show enhanced ribonuclease activity compared with non-infected control cells. 

The importance of defining new antiviral agents chemically was demonstrated in recent stiidies on the antiviral substances isolated from penicillin molds. The antiviral activities of helenine (isolated from Penicillium funiculosian) and statalon (isolated from P. stoloniferum and previously claimed to be an ionic polysaccharide), have been shown to be due to the piresence in these molds of dotible-stranded RNA, a replicative form of RNA found in viral infection. Polyhedral viruses have recently been detected in both strains. ... 

Hilleman and his co-workers have demonstrated interferon production following the administration of reovirus RNA or the replicative form of RNA isolated from E. coli infected with MS2 coliphage. These BNAs are effective in inducing resistance to virus infection m vitro and vivo. The induction of interferon and the broad-spectrum protection against viral infection conferred by double-stranded RNA suggested the use of synthetic polynucleotides, including polyriboinosinic-polyribocytidilic acid, which possess a double-stranded conformation. Chemically modified RNA may also induce the production of interferon. ... 

After penetrating into bacterial cells the DNA of this phage undergoes the typical fate which we saw for RNA in cases of virus reproduction considered above it is replicated by complementary synthesis with the preliminary formation of double-stranded DNA. This process was discovered in later experiments (Sinsheimer, 1961 Sinsheimer et al., 1962) by fractionation of nitrogen- and phosphorus-labeled DNA of infected cells in a density gradient of cesium chloride at various times after infection. This double-stranded form of phage DNA was called the replicative form (RF). 

The formation of the replicative double-stranded form of DNA can therefore be regarded as the first act in molecular morphogenesis of this virus. The replicative form also has infective properties, i.e., it preserves the complete program of phage development. 

The consequence of ADA deficiency is accumulation of adenosine and 2 -deoxyadenosine, substances toxic to lymphocytes, important cells in the immune response. 2 -Deoxyadenosine is particularly toxic because its presence leads to accumulation of its nucleotide form, dATP, an essential substrate in DNA synthesis. Elevated levels of dATP actually block DNA replication and cell division by inhibiting synthesis of the other deoxynncleoside 5 -triphosphates (see Chapter 27). Accumulation of dATP also leads to selective depletion of cellular ATP, robbing cells of energy. Children with ADA SCID fail to develop normal immune responses and are susceptible to fatal infections, unless kept in protective isolation. 

Extracts from 152 plant species, representing 46 different families, were screened for effects on tobacco mosaic virus (TMV) replication in cucumber cotyledons. Twenty species have shown enough activity to warrant further study. Several members of the Caprifoliaceae family increased virus replication. An extract of Lonicera involucrata enlarged the virus lesions in local lesion hosts and produced a thirty fold increase in virus titer, but had no effect on virus replication in systemic hosts. The active material appears to affect the virus defense mechanism of local lesion hosts. An extract of common geranium is an active virus inhibitor. It inactivates TMV and TMV-RNA (ribonucleic acid) in vitro by forming non-infectious complexes. In vivo, it also inhibited starch lesion formation in cucumber cotyledons incited by TMV infection. 

Hepatitis is acute or chronic inflammation of the liver, which is frequently caused by infection with hepato-tropic viruses. Several forms of viral hepatitis (A, B, C, D, E) are known, which result from infection with viruses belonging to separate virus families, differing in their genomic organization, replication strategies, morphology and modes of transmission. 

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