PMID- 12429523
OWN - NLM
STAT- MEDLINE
DCOM- 20021209
LR  - 20190714
IS  - 0042-6822 (Print)
IS  - 0042-6822 (Linking)
VI  - 302
IP  - 1
DP  - 2002 Oct 10
TI  - Infection of BALB/c mice with a herpes simplex virus type 1 recombinant virus 
      expressing IFN-gamma driven by the LAT promoter.
PG  - 144-54
AB  - A recombinant herpes simplex virus type 1 expressing murine interferon-gamma 
      (IFN-gamma) was constructed (HSV-IFN-gamma) to study the effect of IFN-gamma 
      expression on HSV-1 infection of mice. HSV-IFN-gamma was created by inserting the 
      gene for murine IFN-gamma under the control of the latency-associated transcript 
      (LAT) promoter in a LAT-negative recombinant virus. ELISA analysis confirmed that 
      the recombinant virus expressed high levels of IFN-gamma in tissue culture. The 
      recombinant HSV-IFN-gamma had reduced virulence compared with the wild-type and 
      LAT(-) parental strains as judged by death following ocular and ip infections in 
      BALB/c mice. Replication of HSV-IFN-gamma was wild type in tissue culture and 
      mouse eyes. In addition, peak HSV-IFN-gamma titers in mouse trigeminal ganglia 
      (TG) and brain were similar for all viruses, although HSV-IFN-gamma appeared in 
      the TG and brains of ocularly infected mice earlier than either parental virus. 
      Following stimulation with UV-inactivated virus, lymphocytes from 
      HSV-IFN-gamma-infected mice appeared to produce a steady level of interleukin-2 
      (IL-2) and IFN-gamma throughout the first week of infection, while the IL-2 and 
      IFN-gamma levels in lymphocytes from wild-type and the LAT-negative parental 
      virus, dLAT2903, varied over time. Also in contrast to lymphocytes from wild-type 
      and dLAT2903-infected mice, lymphocytes from HSV-IFN-gamma-infected mice produced 
      no detectable IL-4. Following stimulation with recombinant IFN-gamma 
      (rIFN-gamma), lymphocytes from HSV-IFN-gamma-infected mice produced higher levels 
      of IFN-gamma, as compared to lymphocytes from control virus-infected mice. 
      Finally, CTL and cell proliferation induced by HSV-IFN-gamma were similar to 
      those of both parental viruses. Thus, this report demonstrates that (i) 
      HSV-IFN-gamma had reduced neurovirulence, despite having enhanced replication in 
      the TG of infected mice; (ii) HSV-IFN-gamma did not enhance CTL activity above 
      that seen in wild-type infected mice; and (iii) HSV-IFN-gamma induced a T(H)1 
      pattern of cytokine response.
FAU - Ghiasi, Homayon
AU  - Ghiasi H
AD  - Ophthalmology Research, Cedars-Sinai Burns & Allen Research Institute, Los 
      Angeles, California 90048, USA. ghiasih@cshs.org
FAU - Osorio, Yanira
AU  - Osorio Y
FAU - Hedvat, Yahya
AU  - Hedvat Y
FAU - Perng, Guey Chuen
AU  - Perng GC
FAU - Nesburn, Anthony B
AU  - Nesburn AB
FAU - Wechsler, Steven L
AU  - Wechsler SL
LA  - eng
GR  - EY09224/EY/NEI NIH HHS/United States
GR  - EY13615/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (Interleukin-2)
RN  - 207137-56-2 (Interleukin-4)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Brain/immunology/pathology/virology
MH  - Cell Division
MH  - Cell Line
MH  - Eye/immunology/virology
MH  - Female
MH  - Gene Expression
MH  - Herpes Simplex/*immunology/pathology/virology
MH  - Herpesvirus 1, Human/genetics/immunology/physiology
MH  - Humans
MH  - Interferon-gamma/biosynthesis/genetics/*immunology/pharmacology
MH  - Interleukin-2/biosynthesis
MH  - Interleukin-4/biosynthesis
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Promoter Regions, Genetic
MH  - Recombination, Genetic
MH  - Solubility
MH  - T-Lymphocytes, Cytotoxic/cytology/immunology
MH  - Tears/immunology/virology
MH  - Trigeminal Ganglion/immunology/pathology/virology
MH  - Virulence
MH  - Virus Replication
EDAT- 2002/11/14 04:00
MHDA- 2002/12/10 04:00
CRDT- 2002/11/14 04:00
PHST- 2002/11/14 04:00 [pubmed]
PHST- 2002/12/10 04:00 [medline]
PHST- 2002/11/14 04:00 [entrez]
AID - S0042682202916090 [pii]
AID - 10.1006/viro.2002.1609 [doi]
PST - ppublish
SO  - Virology. 2002 Oct 10;302(1):144-54. doi: 10.1006/viro.2002.1609.