The outcome of herpes simplex virus type 1 (HSV-1) infection depends upon the interplay of both host and viral factors. During lytic infection, HSV-1 causes a loss of immunofluorescent staining of discrete nuclear domains (ND10). This elimination of the host's ND10 staining occurs under conditions that allow only HSV-1 immediate early viral gene expression. Western blot analysis indicates that the loss of ND10 staining is due to ND 10 redistribution, rather than protein degradation or turnover. When deletion mutants of all of the HSV-1 immediate early genes were tested, only infection with an immediate early gene 1 product (ICP0) deletion mutant, d11403, was unable to eliminate ND10 antigen staining. Also, ICP0 transiently colocalized with ND10 antigens, after which ND10 antigens became undetectable. At late times during infection with d11403, the host ND 10 antigens were retained in virus-induced structures which were never observed during wild-type HSV-I infection. These results suggested that ICP0 may be directly involved in the modification of the host nuclear domain. Infection with an adenovirus recombinant that expressed ICP0 demonstrated that in the absence of other HSV-1 proteins ICP0 was sufficient for the change in nuclear distribution of host antigens located at ND 10. We postulate that the trans-activation function of ICP0 during viral replication may be mediated by replacing, modifying or reorganizing nuclear host factors.

A latent infection can be established in the trigeminal ganglia of mice after corneal inoculation of herpes simplex virus type 1 (HSV-1). With a virion DNA probe, three transcripts (2.0, 1.5, and 1.45 kilobases [kb]) were detected by Northern blot (RNA blot) analysis of RNAs isolated from the ganglia of latently infected mice. All three transcripts hybridized to a nick-translated HSV-1 DNA probe from BamHI restriction fragment B (strain F). These RNAs were mapped with subfragments of BamHI-B and with strand-specific probes. They are at least partially colinear with each other, map to a 3.0-kb PstI-MluI subfragment of BamHI-B, and are transcribed from left to right. The latent HSV-1 RNAs partially overlap the 3' end of ICPO mRNA but are transcribed in the opposite direction. The latent RNAs were not as extensively poly(A) + as actin mRNA. The HSV-1 transcripts detected in latently infected trigeminal ganglia did not correspond with any that have been previously identified in permissively infected cells in tissue culture. However, the 2.0-kb HSV-1 RNA present during latency was detectable at reduced levels in the trigeminal ganglia of acutely infected mice and in infected tissue culture cells. The data indicate that the pattern of viral gene expression during HSV-1 latency in the trigeminal ganglia of mice does not represent restriction of the genes actively transcribed during the lytic replication cycle in tissue culture.

RNA from an immediate early region of the type 1 herpes simplex virus genome is present in the trigeminal ganglia of latently infected mice ( ABSTRACT Transcription of the type 1 herpes simplex virus (HSV-1) genome in trigeminal ganglia of latently Infected mice was studied using in situ hybridization. Probes representative of each temporal gene class were used to determine the regions of the genome that encode the transcripts present in latently infected cells. Probes encoding HSV-1 sequences of the five immediate early genes and representative early (thymidine kinase), early-late (major capsid protein), and late (glycoprotein C) genes were used in these experiments. Of the probes tested, only those encoding the immediate early gene product infected-cell polypeptide (ICP) 0 hybridized to RNA in latently infected tissues. Probes containing the other immediate

The herpes simplex virus type 1 (HSV‐1) transcripts that can be detected during latent infection by Northern blot analysis in human and experimental animal sensory ganglia are encoded by diploid genes. To investigate their role in latent infection we studied HSV‐1 variant 1704, which has deleted most of the IRL copy of the coding region of these RNAs and has a 1.2‐kb deletion that is immediately upstream of the coding region of the TRL copy. During primary infection, 1704 replicated in trigeminal ganglia with kinetics similar to the parent virus (17+) and established latent infection. However, while explant reactivation of latent HSV‐1 from trigeminal ganglia was detected in 100% of 17+ infected mice within 7 days, the reactivation of 1704 was significantly delayed, and 31 days elapsed before eight out of nine mice became virus positive. The recognized HSV‐1 latency‐associated RNAs were not detected during the latent state of 1704 by Northern blot analysis or in situ hybridization, which implies that the 1.2‐kb deletion may contain the promoter or other important regulatory elements. The data indicate that detectable levels of these latency‐associated transcripts are not required for viral replication, establishment, or maintenance (greater than 6 weeks) of HSV‐1 latency in trigeminal ganglia, but suggest a role in reactivation.

BACKGROUND Weight-for-length (WFL) is currently used to assess adiposity under 2 years. We assessed WFL- versus BMI-based estimates of adiposity in healthy infants in determining risk for early obesity. METHODS Anthropometrics were extracted from electronic medical records for well-child visits for 733949 full-term infants from a large pediatric network. World Health Organization WFL and BMI z scores (WFL-z and BMI-z, respectively) were calculated up to age 24 months. Correlation analyses assessed the agreement between WFL-z and BMI-z and within-subject tracking over time. Logistic regression determined odds of obesity at 2 years on the basis of adiposity classification at 2 months. RESULTS Agreement between WFL-z and BMI-z increased from birth to 6 months and remained high thereafter. BMI-z at 2 months was more consistent with measurements at older ages than WFL-z at 2 months. Infants with high BMI (≥85th percentile) and reference WFL (5th–85th percentiles) at 2 months had greater odds of obesity at 2 years than those with high WFL (≥85th percentile) and reference BMI (5th–85th percentiles; odds ratio, 5.49 vs 1.40; P < .001). At 2 months, BMI had a higher positive predictive value than WFL for obesity at 2 years using cut-points of either the 85th percentile (31% vs 23%) or 97.7th percentile (47% vs 29%). CONCLUSIONS High BMI in early infancy is more strongly associated with early childhood obesity than high WFL. Forty-seven percent of infants with BMI ≥97.7th percentile at 2 months (versus 29% of infants with WFL ≥97.7th percentile at 2 months) were obese at 2 years. Epidemiologic studies focused on assessing childhood obesity risk should consider using BMI in early infancy.