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Lawrence Corey

Publications and source records attributed to Lawrence Corey.

138 records · Page 8Linked to original sources
PubMed2002

Human herpesvirus 6 infection in febrile infants ninety days of age and younger.

BACKGROUND: The importance of human herpesvirus 6 (HHV-6) as a pathogen in febrile infants </=90 days of age is unknown. OBJECTIVE: To determine whether febrile infants 90 days of age and younger evaluated for sepsis have evidence of HHV-6 DNA in plasma or cerebrospinal fluid (CSF). METHODS: Febrile infants </=90 days of age were tested for HHV-6 DNA using a real time quantitative fluorescent probe polymerase chain reaction assay. RESULTS: Eighty samples from 47 infants were tested for HHV-6 DNA; 5 of 47 infants (10.6%) had HHV-6 DNA in plasma. In 2 of the 5 infants with HHV-6 DNA in plasma, HHV-6 DNA was also detected in the CSF. Both infants with evidence of HHV-6 DNA in plasma and CSF had HHV-6 Variant A infection. The quantity of HHV-6 DNA detected ranged from 70 to 169,000 DNA copies/ml. One infant with HHV-6 variant B infection had concomitant Escherichia coli bacteremia and urinary tract infection. CONCLUSIONS: Approximately 10% of febrile infants </=90 days of age evaluated for sepsis had evidence of HHV-6 infection. HHV-6 Variant A and B infections were seen in these young infants. HHV-6 DNA was found in infants with and without another explanation for fever. Quantification of viral DNA may be important in determining the relevance of HHV-6 DNA in clinical specimens.

Aging↗
PubMed2002

Potential benefits of a serodiagnostic test for herpes simplex virus type 1 (HSV-1) to prevent neonatal HSV-1 infection.

BACKGROUND: Changes in sexual practices have led to an increase in the incidence of genital herpes simplex virus type 1 (HSV-1) infections. Such infections affect an estimated 400 newborns each year, with serious consequences. GOAL: To evaluate the use of a serodiagnostic test for HSV-1 to be used by pregnant women, and possibly their sexual partners, in preventing neonatal HSV-1 infections by identifying seronegative (at-risk) women. STUDY DESIGN: The number of cases of neonatal HSV-1 prevented by a test of a given sensitivity and specificity is estimated using two simple models parameterized with data from published sources. RESULTS: Used by women only, a 90%-specific test for HSV-1 could avert 71%-90% of the expected cases of infection among women using the test, requiring about 14,000 tests per case averted. This result depends linearly on the specificity of the test and does not depend on the sensitivity. Use by women and their partners results in more tests for the same benefit (about 24,000 tests per case averted if the test is 90% sensitive and 90% specific), because the only additional information provided by testing the partner of an at-risk woman is to determine that her partner may not be HSV-1 positive. CONCLUSIONS: The key feature of such a diagnostic test is its specificity; its use to identify at-risk women could provide public health benefits if the specificity exceeds 70%, but these benefits would increase dramatically for higher specificities. Use of such a test for couples is likely to be more costly and less effective than testing women only.

Adult↗
PubMed2002

Assessment of a combined testing strategy for detection of antibodies to human herpesvirus 8 (HHV-8) in persons with Kaposi's sarcoma, persons with asymptomatic HHV-8 infection, and persons at low risk for HHV-8 infection.

The performance of a human herpesvirus 8 (HHV-8) enzyme immunoassay (EIA) and selective subsequent use of an HHV-8 immunofluorescence assay (IFA) was tested in persons unlikely to be infected with HHV-8 and those who had HHV-8 detected in their saliva. The IFA was performed on samples within a range of EIA optical densities (0.15 to 0.35) where there was considerable overlap between HHV-8-infected and uninfected individuals. The sensitivity of the testing strategy was 88%, with a specificity of 97%.

Antibodies, Viral↗
PubMed2002

Quantitative stability of DNA after extended storage of clinical specimens as determined by real-time PCR.

Viral DNA stored for extended periods can be amplified by PCR. However, it is unknown whether stored specimens give accurate quantitative results by newer real-time PCR techniques. We therefore compared herpes simplex virus DNA levels in specimens before and after 16 months of storage. The levels of viral DNA remained stable whether the DNA was stored as purified DNA or unextracted DNA in a whole specimen.

AIDS-Related Opportunistic Infections↗
PubMed2002

Evidence for human immunodeficiency virus type 1 replication in vivo in CD14(+) monocytes and its potential role as a source of virus in patients on highly active antiretroviral therapy.

In vitro studies show that human immunodeficiency virus type 1 (HIV-1) does not replicate in freshly isolated monocytes unless monocytes differentiate to monocyte-derived macrophages. Similarly, HIV-1 may replicate in macrophages in vivo, whereas it is unclear whether blood monocytes are permissive to productive infection with HIV-1. We investigated HIV-1 replication in CD14(+) monocytes and resting and activated CD4(+) T cells by measuring the levels of cell-associated viral DNA and mRNA and the genetic evolution of HIV-1 in seven acutely infected patients whose plasma viremia had been <100 copies/ml for 803 to 1,544 days during highly active antiretroviral therapy (HAART). HIV-1 DNA was detected in CD14(+) monocytes as well as in activated and resting CD4(+) T cells throughout the course of study. While significant variation in the decay slopes of HIV-1 DNA was seen among individual patients, viral decay in CD14(+) monocytes was on average slower than that in activated and resting CD4(+) T cells. Measurements of HIV-1 sequence evolution and the concentrations of unspliced and multiply spliced mRNA provided evidence of ongoing HIV-1 replication, more pronounced in CD14(+) monocytes than in resting CD4(+) T cells. Phylogenetic analyses of HIV-1 sequences indicated that after prolonged HAART, viral populations related or identical to those found only in CD14(+) monocytes were seen in plasma from three of the seven patients. In the other four patients, HIV-1 sequences in plasma and the three cell populations were identical. CD14(+) monocytes appear to be one of the potential in vivo sources of HIV-1 in patients receiving HAART.

Amino Acid Sequence↗
PubMed2002

Selection for human immunodeficiency virus type 1 recombinants in a patient with rapid progression to AIDS.

Although human immunodeficiency virus type 1 (HIV-1) recombinants have been found with high frequency, little is known about the forces that select for these viruses or their importance to pathogenesis. Here we document the emergence and dynamics of 11 distinct HIV-1 recombinants in a man who was infected with two subtype B HIV-1 strains and progressed rapidly to AIDS without developing substantial cellular or humoral immune responses. Although numerous frequency oscillations were observed, a single recombinant lineage eventually came to dominate the population. Numerical simulations indicate that the successive recombinant forms displaced each other too rapidly to be explained by any simple model of random genetic drift or sampling variation. All of the recombinants, including several resulting from independent recombination events, possessed the same sequence motif in the V3 loop, suggesting intense selection on this segment of the viral envelope protein. The outgrowth of the predominant V3 loop recombinants was not, however, associated with changes in coreceptor utilization. The final variant was instead notable for having lost 3 of 14 potential glycosylation sites. We also observed high ratios of synonymous-to-nonsynonymous nucleotide changes-suggestive of purifying selection-in all viral populations, with particularly high ratios in newly arising recombinants. Our study, therefore, illustrates the unusual and important patterns of viral adaptation that can occur in a patient with weak immune responses. Although it is hard to tease apart cause and effect in a single patient, the correlation with disease progression in this patient suggests that recombination between divergent viruses, with its ability to create chimeras with increased fitness, can accelerate progression to AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Virus population homogenization following acute human immunodeficiency virus type 1 infection.

Understanding the properties of human immunodeficiency virus type 1 (HIV-1) variants capable of establishing infection is critical to the development of a vaccine against AIDS. Previous studies of men have shown that the HIV-1 env gene is homogeneous early in infection, leading to the suggestion that infection is established by a single transmitted variant. However, we report here that all of eight homosexual men evaluated beginning 3.7 to 9 weeks following onset of symptoms of acute infection harbored diverse virus populations in their blood, with median genetic distances averaging 1.08% in the env C2V5 region and 0.81% in the gag p17 gene. Within another 4.7 to 11 weeks, the variant lineage in env became more homogeneous, while gag sequences continued to diversify. Thus, the homogenization that has been reported to characterize acute infection is actually preceded by the replication of multiple virus variants. This early selective process focuses on viral properties within Env but not Gag p17. Hence, the viral homogeneity observed early in HIV-1 infection results from a selective process that occurs during the establishment of infection.

Acute Disease↗
PubMed2002

Expression of cutaneous lymphocyte-associated antigen by CD8(+) T cells specific for a skin-tropic virus.

Virus-specific CD8(+) T cells traffic to infected tissues to promote clearance of infection. We used herpes simplex virus type 2 (HSV-2) as a model system to investigate CD8(+) T cell trafficking to the skin in humans. Using human leukocyte antigen (HLA) class I tetramers, we observed that HSV-specific CD8(+) T cells in the peripheral blood expressed high levels of cutaneous lymphocyte-associated antigen (CLA). In contrast, CD8(+) T cells specific for non-skin-tropic herpesviruses lacked CLA expression. CLA-positive HSV-2-specific CD8(+) T cells had the characteristics of central memory cells, expressing CCR7, CD62L, and CD28, and they proliferated briskly in response to antigen. CLA is related to a functional E-selectin ligand, and both E-selectin and CLA-positive cells were detected in HSV-2-infected skin. HSV-2-specific T cells adhered to cells transfected with E-selectin. A higher proportion of HSV-specific CD8(+) T cells recovered from herpes lesions express CLA compared with blood, consistent with a role for CLA in skin homing. To our knowledge, this is the first report of expression of tissue-specific adhesion-associated molecules by virus-specific CD8(+) T cells. The evaluation of vaccines for skin and mucosal pathogens should include study of the induction of appropriate tissue-specific homing molecules.

Animals↗
PubMed2001

Effect of antivirals on human herpesvirus 6 replication in hematopoietic stem cell transplant recipients.

Human herpesvirus 6 (HHV-6) appears to cause central nervous system (CNS) syndromes, especially in hematopoietic stem cell transplant (HSCT) recipients. We reviewed our experience with HHV-6-associated CNS disease to evaluate both the clinical and virological presentation and response to antiviral therapy. A search of our virology database from January 1998 through June 2000 identified 11 HSCT recipients who had HHV-6 DNA detected by polymerase chain reaction in cerebrospinal fluid (CSF); 8 of whom had CNS dysfunction without another clear etiology identified. HHV-6 levels in serum and CSF were evaluated before and after ganciclovir and/or foscarnet therapy. Median log HHV-6 CSF levels appeared to decrease over time concurrent with antiviral therapy (serum level, 2.0 vs. 0 copies/mL [P=.38]; CSF level, 4.4 vs. 2.0 copies/mL [P=.13], sign test). Our data suggests that HHV-6 may cause moderate to severe CNS disease after HSC transplantation. Prospective studies are needed to define the spectrum of HHV-6-associated disease and to determine whether antiviral therapy offers clinical benefit.

Adolescent↗
PubMed2001

Search for polymorphisms in the genes for herpesvirus entry mediator, nectin-1, and nectin-2 in immune seronegative individuals.

Recently, individuals have been identified who possess T cell responses to herpes simplex virus (HSV) antigens despite the absence of detectable anti-HSV antibodies in their serum. The significance of this immune seronegative status is unclear, but it could indicate resistance to overt HSV infection. The aims of the present study were to investigate whether genetic differences in receptors used by HSV for cell entry (herpesvirus entry mediator [HVEM], nectin-1, and nectin-2) could be detected in immune seronegative individuals. Coding polymorphisms were identified in the HVEM and nectin-1 genes. The variant receptor proteins were expressed, and their ability to bind the viral ligand glycoprotein D and to mediate HSV entry after transient transfection into normally resistant cells was compared with that of their wild-type counterparts. HSV entry activity in wild-type and variant forms of the receptors was indistinguishable, which indicates that the polymorphisms observed are unlikely to explain the possible restrictions on HSV replication or spread in immune seronegative individuals.

Animals↗
PubMedDate not supplied

HHV-8 infection: a model for reactivation and transmission.

The rapid pace of knowledge about HHV-8 since its discovery has been one of the most exciting aspects of medical virology in the last decade. As outlined in this review, the discovery by Drs Chang and Moore of this virus has opened up a broad field of biology with interesting contrasts between current epidemiological data for Kaposi's sarcoma and the cell biology of this gamma herpesvirus. In particular, we summarise the paucity of virological data supporting genital sites of replication and emphasise detection of HHV-8 in the oropharynx. Hopefully continued study will address many of the critical questions that exist today regarding how this infection is transmitted and acquired.

Animals↗