Congenital Cytomegalovirus Infection: A Fifteen Year Perspective

Hanshaw, James B.

doi:10.1093/infdis/123.5.555

Cited by 217 publications

(91 citation statements)

References 22 publications

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“…Some congenital infections are symptomless, and at birth only a few congenitally infected babies show typical severe cytomegalic inclusion body disease (CID) with hepatosplenomegaly, thrombocytopenia, seizures, chorioretinitis, etc. (Starr et al, 1970;Hanshaw, 1971). Previous investigations also indicate that CMV infection is very common in the first months of life.…”

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Perinatal Cytomegalovirus Infection in Man

Granström¹,

Leinikki²,

Santavuori³

et al. 1977

Neuropediatrics

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SUMMARY In a prospective study of 148 children from urbanized southern Finland 3 were found to be congenitally and 48 perinatally infected with cytomegalovirus (CMV), while 6 developed 'late' infection during the first year of life. During pregnancy and the first year after delivery 23 of the mothers had no CMV antibodies; none of the children of these seronegative mothers developed any type of CMV infection. Fresh blood exchange transfusions did not increase the risk of CMV infection. The data support the hypothesis that the mother is the source of perinatal CMV infection. Children with a low birthweight not due to prematurity, and first children seem to run a greater risk of acquiring perinatal CMV infection. If the child is breast fed up to the age of 2 months the risk seems to be increased. Perinatal CMV infection gave rise to no symptoms or signs and had no effect on growth or on motor and psychosocial development during the first year of life.

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confidence: 96%

Perinatal Cytomegalovirus Infection in Man

Granström¹,

Leinikki²,

Santavuori³

et al. 1977

Neuropediatrics

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“…In contrast, HCMV infection leads to significant morbidity and mortality in the immunocompromised. HCMV is an important opportunistic pathogen in AIDS patients (16)(17)(18)(19)(20), is a leading infectious cause of complications in transplant recipients (21-28), and causes severe neurological disease in congenitally infected neonates (29)(30)(31)(32)(33)(34).HCMV pathogenesis and disease result from viral spread to multiple organ sites following primary HCMV infection, a process which appears to be a critical step in the viral persistence strategy, as it allows for the establishment of lifelong persistence within the host, as well as for viral shedding and spread to additional hosts (1,35,36). Monocytes are the primary blood-borne targets for HCMV infection and are thought to be centrally involved in the hematogenous dissemination of the virus to target organ systems (37-41).…”

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Human Cytomegalovirus Promotes Survival of Infected Monocytes via a Distinct Temporal Regulation of Cellular Bcl-2 Family Proteins

Collins-McMillen

Kim

Nogalski

et al. 2016

J Virol

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Monocytes IMPORTANCEHematogenous dissemination of HCMV via infected monocytes is a crucial component of the viral survival strategy and is required for the establishment of persistent infection and for viral spread to additional hosts. Our system of infected primary human blood monocytes provides us with an opportunity to answer specific questions about viral spread and persistence in in vivo-relevant myeloid cells that cannot be addressed with the more traditionally used replication-permissive cells. Our goal in examining the mechanisms whereby HCMV reprograms infected monocytes to promote viral dissemination is to uncover new targets for therapeutic intervention that would disrupt key viral survival and persistence strategies. Because of this important role in maintaining survival of HCMV-infected monocytes, our new data on the role of Bcl-2 regulation during viral infection represents a promising molecular target for mitigating viral spread and persistence. H uman cytomegalovirus (HCMV) is a ubiquitous host-restricted betaherpesvirus that infects 60 to 90% of the population and persists for the lifetime of the infected individual (1). HCMV infection results in a wide range of pathogenic outcomes dependent upon the age and immune status of the host (2). Infection of immunocompetent hosts is usually asymptomatic or only mildly symptomatic (3, 4); however, it can cause infectious mononucleosis, is a risk factor for the development of cardiovascular disease (5-9), and has been linked to certain types of cancers in otherwise healthy individuals (10-15). In contrast, HCMV infection leads to significant morbidity and mortality in the immunocompromised. HCMV is an important opportunistic pathogen in AIDS patients (16)(17)(18)(19)(20), is a leading infectious cause of complications in transplant recipients (21-28), and causes severe neurological disease in congenitally infected neonates (29)(30)(31)(32)(33)(34).HCMV pathogenesis and disease result from viral spread to multiple organ sites following primary HCMV infection, a process which appears to be a critical step in the viral persistence strategy, as it allows for the establishment of lifelong persistence within the host, as well as for viral shedding and spread to additional hosts (1,35,36). Monocytes are the primary blood-borne targets for HCMV infection and are thought to be centrally involved in the hematogenous dissemination of the virus to target organ systems (37-41). We propose that HCMV reprograms the biology of infected monocytes, creating the ideal cell type to serve as "Trojan horses" to carry HCMV to target host organ sites and then to

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“…Human cytomegalovirus (HCMV), a member of the herpesvirus family, is the etiologic agent of a wide spectrum of human diseases (1,2). Upon infection, the HCMV genes are expressed in three sequential phases (reviewed in ref.…”

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Binding of transcription factors and creation of a large nucleoprotein complex on the human cytomegalovirus enhancer.

Ghazal¹,

Luboń²,

Fleckenstein³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

116

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The effect of the human cytomegalovirus immediate early region 1 enhancer on transcription was studied in vitro with HeLa cell nuclear extract. Stimulation of in vitro transcription mediated by the enhancer element involves its recognition by specific trans-acting factors present in the nuclear extract. DNase I protection analysis was used to determine at the nucleotide level those enhancer sequences that interact with nuclear factors. At least nine sites of protein-DNA interaction were detected over -400 base pairs of enhancer sequence. The regions of nuclease protection are associated with 21-, 19-, 18-, and 17-base-pair repeat elements as well as with a unique sequence, creating a large nucleoprotein complex. The relationship between the protein binding and the activity of the immediate early region 1 enhancer is discussed.Human cytomegalovirus (HCMV), a member of the herpesvirus family, is the etiologic agent of a wide spectrum of human diseases (1, 2). Upon infection, the HCMV genes are expressed in three sequential phases MATERIALS AND METHODS Preparation of DNA. The recombinant plasmids pPSCAT, pSSCAT and pCMV(-524)CAT, pCMV(-65)CAT were obtained from J. Nelson and R. Ruger, respectively. These constructs contain various 5'-flanking sequences of the HCMV (strain AD169) IEJ gene linked to the bacterial chloramphenicol acetyltransferase gene (see Fig. 1A). Plasmids pE1, pE2, and pE3 contain BAL-31 deletion fragments (prepared by R. Ruger) overlapping the enhancer and promoter region of the IEJ gene that were cloned into the HindIII and BamHI sites of pTZl8R (see Fig. 1A). The competitor fragments (El, E2, and E3) were gel-purified from their respective plasmids after cleavage with EcoRd and HindIII restriction enzymes.Nuclear Extract Preparation and Fractionation. Nuclear extract from HeLa cells was prepared as described by Dignam et al. (20). The fractionation of the nuclear extract on columns of heparin-agarose (Bio-Rad) and DEAE-Sepharose CL-6B (Pharmacia) was performed according to the procedure of Dynan and Tjian (21). The heparin-agarose and DEAE-Sepharose columns were step-washed with 0.4 M and 0.225 M KCl, respectively, The flow-through fractions (HAO.1, DEO.1) and the step-washed fractions (HAO.4, DEO.225) from the column chromatography were used in the DNase I protection analysis.In Vitro Transcription Assays. RESULTSThe HCMV IEJ Gene Promoter Is Transcriptionally Active in Vitro. Run-off assays were performed to determine whether the crude nuclear extract prepared from the nuclei of uninfected HeLa cells contained the necessary factors for initiating and sustaining transcription from the HCMV IEl promoter. The DNA templates pPSCAT and pSSCAT, containing the IEl promoter and 5'-flanking region, were cleaved with the restriction endonucleases Pvu II or EcoRI, which truncate the template 165 or 260 base pairs downstream of the IEl cap site, respectively, generating run-off transcripts that could be visualized by electrophoresis. For all the templates tested, the size of the run-off transc...

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Congenital Cytomegalovirus Infection: A Fifteen Year Perspective

Cited by 217 publications

References 22 publications

Perinatal Cytomegalovirus Infection in Man

Perinatal Cytomegalovirus Infection in Man

Human Cytomegalovirus Promotes Survival of Infected Monocytes via a Distinct Temporal Regulation of Cellular Bcl-2 Family Proteins

Binding of transcription factors and creation of a large nucleoprotein complex on the human cytomegalovirus enhancer.

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