REPLIKASI VIRUS

Sekilas Replikasi

Hal ini mudah untuk memulai bagian ini pada replikasi virus dengan pandangan mata burung dari
peristiwa besar dari HSV replikasi (Gambar. 3).

FIG. 3. Diagram of the replication cycle of HSV. At the upper left, the virion binds to the cell plasma
membrane, and the virion envelope fuses with the plasma membrane, releasing the capsid and
tegument proteins into the cytoplasm. The vhs protein acts to cause degradation of mRNAs. The
capsid is transported to the nuclear pore, where the viral DNA is released into the nucleus. The viral
DNA circularizes and is transcribed by host RNA polymerase II to give first the IE or a mRNAs. IE gene
transcription is stimulated by the VP16 tegument protein. Five of the six IE proteins act to regulate
viral gene expression in the nucleus. They transactivate E or b gene transcription. The E proteins are
involved in replicating the viral DNA molecule. Viral DNA synthesis stimulates L or g gene expression.
The L proteins are involved in

perakitan kapsid dalam inti dan memodifikasi membran untuk pembentukan virion. tunas kapsid
diisi melalui membran dalam membentuk virion menyelimuti, dan keluar virion dari sel dengan
mekanisme yang dijelaskan pada bagian Majelis Virion dan Egress.

Untuk memulai infeksi, virus harus melampirkan ke sel reseptor permukaan. Fusi dari amplop
dengan membran plasma cepat berikut lampiran awal. Struktur tegument-kapsid deenveloped
kemudian diangkut ke pori-pori nuklir, di mana DNA dilepaskan ke dalam inti.

Transkripsi dari genom virus, replikasi DNA virus, dan perakitan kapsid baru berlangsung di inti. DNA
virus ditranskripsi seluruh infeksi produktif dengan RNA polimerase tuan II, namun dengan
partisipasi dari faktor virus pada semua tahap infeksi. Sintesis produk gen virus diatur secara ketat:
ekspresi gen virus yang terkoordinasi diatur dan berurutan memerintahkan secara cascade. Produk
gen dipelajari untuk bentuk tanggal setidaknya lima kelompok sebagai akibat dari kedua regulasi
transkripsi dan posttranscriptional.

Beberapa produk gen adalah enzim-enzim dan protein DNA-mengikat terlibat dalam replikasi DNA
virus. Sebagian besar DNA virus disintesis oleh mekanisme rolling-lingkaran, menghasilkan
concatemers, yang dibelah menjadi monomer selama proses perakitan nukleokapsid.

Assembly occurs in several stages. After packaging of DNA into preassembled capsids, the virus
matures and acquires infectivity by budding through the inner lamella of the nuclear membrane. The
transit of virions from the space between the inner and outer nuclear membranes to the subcellular
space is less well defined. It has been suggested that the virion envelope is processed by transit
through Golgi stacks or by being deenveloped and then reenveloped at the trans-Golgi network. In
fully permissive tissue culture cells, the entire process takes about 18 to 20 hours.

Virus Attachment and Entry

Masuknya HSV ke dalam sel dipengaruhi dalam tiga tahap (Gambar. 4). Yang pertama melibatkan
lampiran dari virion ke permukaan sel. Langkah kedua melibatkan interaksi gD dengan salah satu
dari beberapa reseptor seluler. Pada langkah terakhir, amplop virus dan sekering membran plasma
untuk melepaskan struktur kapsid-tegument ke dalam sitoplasma. Sebagian besar informasi tentang
proses ini didasarkan pada studi dari sel nonpolarized di mana protein membran berinteraksi dengan
protein amplop kemungkinan besar didistribusikan secara acak. Lampiran dan masuknya virus ke
dalam terpolarisasi sel-sel epitel yang paling dalam tubuh-mungkin manusia berbeda secara rinci.

ARA. 4. Masuk dan Uncoating dari HSV-1. Yang ditampilkan ultrathin Epon bagian dari sel Vero
terinfeksi dengan HSV-1 pada MOI dari 500 di hadapan cycloheximide (CH). Setelah 2 jam virus
mengikat pada 4 ° C, sel-sel baik segera diperbaiki (a dan b), atau pemanasan selama 30 (c ke f) atau
60 (g dan h) menit. Binding (a dan b). Fitur morfologi utama dari virus utuh terikat pada membran
plasma (PM) adalah amplop virus (b, panah) dengan paku virus (a, panah), kapsid virus (panah), dan
virus genom DNA elektron-padat dalam kapsid. Fusion (c dan d). Setelah pemanasan, amplop virus
sekering dengan membran plasma, dan kapsid (panah) dan protein tegument dilepaskan ke sitosol.
Pelepasan kapsid (e dan f). Persiapan, yang menampilkan kontras yang menonjol dari tegument itu,
menunjukkan bahwa tegument (panah) tetap berada di belakang di PM. Mengikat ke pori nuklir (g
dan h). Pada titik waktu kemudian, capsids (panah) telah tiba di amplop nuklir (NE), di mana mereka
secara eksklusif terletak di aposisi dekat dengan kompleks pori nuklir. Kadang-kadang, serat yang
berasal dari pori-pori (panah) yang terlihat, dimana kapsid muncul untuk mengikat. Hampir semua
capsids di pori-pori nuklir muncul kosong dan telah kehilangan elektron-padat DNA inti. Bar, 100 nm.
(Dari ref. 578, dengan izin). dimana kapsid muncul untuk mengikat. Hampir semua capsids di pori-
pori nuklir muncul kosong dan telah kehilangan elektron-padat DNA inti. Bar, 100 nm. (Dari ref. 578,
dengan izin). dimana kapsid muncul untuk mengikat. Hampir semua capsids di pori-pori nuklir
muncul kosong dan telah kehilangan elektron-padat DNA inti. Bar, 100 nm. (Dari ref. 578, dengan
izin).

The initial attachment to nonpolarized cells involves the interaction of the viral envelope gC, and, to
a lesser extent gB, with the glycosaminoglycan moieties of cell surface heparan sulfate ( 560,686).
Although gC confers the greatest efficiency for attachment in these systems, it is not essential for
either entry or viral replication ( 216).

Lampiran sulfat heparan meningkatkan infeksi tetapi bukan merupakan syarat mutlak untuk infeksi
HSV sel karena sel-sel tanpa sulfat heparan tetapi mengungkapkan glukosaminoglikan lainnya
(misalnya, chondroitin sulfat) dapat terinfeksi. Sel tanpa kedua jenis glikosaminoglikan juga bisa
terinfeksi, meskipun pada efisiensi berkurang (19). Kedua, langkah berurutan, ditunjuk sini sebagai
mengikat coreceptor sebuah, melibatkan interaksi gD dengan salah satu dari beberapa molekul
seluler milik tiga keluarga molekul struktural yang tidak terkait. Seperti yang sering terjadi, mereka
telah diberi sebutan yang berbeda berdasarkan fungsi sel mereka atau fungsi mereka dalam infeksi
virus.

Yang pertama dari coreceptors ini adalah anggota dari keluarga tumor necrosis factor (TNF) reseptor
awalnya disebut virus herpes masuk mediator (HVEM) (392) tapi diganti HveA setelah reseptor
lainnya ditemukan (659). HveA hadir terutama dalam sel limfoid, dan dengan demikian tidak
mungkin berfungsi sebagai mediator utama dari HSV masuk ke dalam sel manusia. Ini berfungsi
sebagai reseptor untuk masuk dari beberapa yang dipilih HSV-1 strain, HSV-2, tetapi tidak untuk
alphaherpesvirus terkait, pseudorabies (PRV) virus (392.670).

The second family of coreceptors belongs to the immunoglobulin superfamily and is related to the
poliovirus receptors (183). The first identified members of this family were named HveB (659) and
HveC (183) and herpesvirus immunoglobulin-like receptor (HIgR) (92). This family includes several
isoforms present in both human and nonhuman cells that are encoded by mRNAs generated by
alternative mRNA splicing. More recently, these cellular proteins have been shown to act as
intercellular adhesion molecules and to be localized at adhesion junctions where their C-terminal
domains bind to L-afadin, a PDZ-binding protein that anchors these molecules to cytoskeleton and
adherens junctions. On the basis of their cellular function, they have been named nectins (617);
therefore, the designations that appear now in the literature are nectin-1a (HveC, Prr1), nectin-1b
(HIgR), nectin-2a (HveB, Prr2), and nectin-2d ( 91,340,586). Nectin-1a and nectin-1b, two splice
variants with a common ectodomain, are broadly expressed in cells of epithelial, fibroblastic, neural,
and hematopoietic origin; in keratinocytes; and in human tissues that are targets of HSV infection,
including skin, brain, and spinal ganglia ( 92,183). They mediate entry of all HSV-1 strains tested,
HSV-2, PRV, and bovine herpes virus 1 (183). They also mediate cell-to-cell spread of HSV (91).
Nectin-2a (HveB) and nectin-2d, also splice variant isoforms, mediate the entry of HSV-2, PRV, and
certain viable mutants of HSV-1, but not of wild-type HSV-1 (340,659). The distribution of this
general class (immunoglobulin superfamily) of receptors in human tissues reflects the susceptibility
of cells to infection and is likely to account for both entry and spread of virus from cell to cell.

Homolognya dari nectins manusia telah ditemukan di berbagai spesies. The homolog murine dari
nectin-1 manusia juga memediasi masuknya HSV-1 dan HSV-2 ke dalam sel murine (382). Hal ini
menimbulkan kemungkinan bahwa kemampuan untuk menggunakan homolognya hewan dari
nectin-jenis protein dapat menjelaskan kisaran inang yang luas dari HSV dalam budaya dan hewan
dari spesies yang berbeda sel. Menariknya, aktivitas reseptor ini dilaporkan berfungsi secara
independen dari gD mengikat (382).

The third family has to date only one member: 3-O-sulfated heparan sulfate (563). The 3-O-sulfated
heparan sulfates are broadly distributed on human cells and tissues and mediate efficient HSV-1 but
not HSV-2 entry ( 563). Whether they can mediate entry into human cells remains to be determined.
It is interesting that either protein molecules or specific sites on heparan sulfate can serve as
receptors for HSV entry.

Langkah terakhir dalam entri adalah perpaduan dari amplop virus dengan membran plasma dari sel
inang. Ada penerimaan yang luar biasa dari hipotesis bahwa hasil infeksi produktif dari masuknya
virus dimediasi oleh fusi amplop dan plasma membran (394). Bukti utama adalah demonstrasi yang
Gi dan GE-reseptor-bisa virus Fc dideteksi pada permukaan sel segera setelah penetrasi virus (430).
Sebaliknya, tubuh bukti menunjukkan bahwa entri dengan endositosis tidak mengakibatkan infeksi
produktif. Dengan demikian, sel-sel mengekspresikan gD internalisasi virus oleh endositosis, tapi
replikasi virus tidak terjadi (58.703).

Current evidence indicates that virus–cell fusion requires the participation of gD ( 326), gB (536), and
the gH-gL heterodimer (164). The exact role of these proteins in the fusion process is unknown, but
one could speculate that the binding of gD to the cellular receptors leads to a rearrangement of viral
proteins on the virion surface, a conformational change in their structure, or both, so that gB, gH/gL,
or both can promote fusion. An additional observation underlying the hypotheses is that cells are
infected with wild-type virus aggregate ( syn+ phenotype), whereas certain viral mutants cause the
cells to fuse (called either syn– or syn phenotype). Syn– mutations map in the genes encoding gB,
gH, and gK and in the UL24 membrane protein (526). The data suggest that these proteins may form
a complex and that mutations in any one of the syn proteins cause a rearrangement or a
conformational change in the complex, resulting in cell fusion (526). For detailed reviews on this
topic, see references 57 and 585.

Studies on viral entry into polarized cells have progressed to a much lesser extent. Current data are
based on studies of viral entry into a few polarized cell lines in culture and on corneal cells in vivo.
These data indicate that attachment to the apical surface is gC dependent, whereas entry through
the basolateral surface is gC independent ( 548), and that gG, a viral glycoprotein with no other
known function, plays a key role in the postattachment entry on the apical surface but is not
essential for basolateral entry (633).

The transition from attached to penetrated virus, as measured by the loss of susceptibility to
neutralization, inactivation by acidic pH, or proteases, is very rapid and occurs within minutes (
121,236).

Transport to the Cell Nucleus

After fusion of the envelope to the plasma membrane, some tegument proteins remain in the
cytoplasm (e.g., vhs, U S11) whereas others are either transported to the nucleus (VP16) or may
remain associated with the capsid (e.g., VP1-2), as discussed later in the text. The capsid with
associated tegument structures is then transported through the microtubular network to the nuclear
pore. The extent of our knowledge of virus transport is limited but can be described as follows:

HSV capsids telah diamati terikat mikrotubulus dalam neuron (343.344.433). Dalam sel kultur,
antibodi spesifik untuk protein kapsid co-pelokalan dengan mikrotubulus setelah masuknya virus
(578). Mikrotubulus depolymerizing agen seperti colchicine dan nocodazole memblokir transportasi
nukleokapsid ke inti sel, dan pelabelan antibodi dynein, motor mikrotubulus-dependent,
menunjukkan bahwa itu melekat HSV capsids (578). penulis mengusulkan bahwa capsids masuk
mengikat mikrotubulus dan menggunakan dynein untuk mendorong mereka untuk inti sel.
Mekanisme yang tepat loading struktur kapsid-tegument ke motor dynein sitoplasma tidak
diketahui, tetapi dua pengamatan yang relevan. Pertama, tak lama setelah infeksi, mikrotubulus di
persimpangan dengan membran plasma menjadi terganggu (657), menunjukkan kemungkinan
bahwa pemuatan struktur kapsid-tegument dapat mempengaruhi interaksi mikrotubulus atau
protein yang berhubungan dengan struktur kognitif dalam membran plasma. penyusunan ulang
lebih luas dari jaringan mikrotubular

take place late in infection. Second, recent studies have shown that the U L34 protein binds the
amino-terminal domain of the intermediate chain 1a of cytoplasmic neuronal dynein and that, in the
presence of nocodazole, which causes the depolymerization of dynein, UL34 protein is not
transported to the nucleus (692). Finally, because the normal dynein motor terminus is at the
microtubule-organizing center, it is not clear how the nucleocapsids ultimately come in apposition
with the nuclear pore complex.

After intracytoplasmic transport, the nucleocapsids accumulate at the nuclear envelope and
associate with the nuclear pore complexes (21,578) (see Fig. 4). At the pore, the nucleocapsid
releases its DNA into the nucleus, leaving an empty capsid at the cytoplasmic side of the complex.
Little is known about the mechanisms of HSV DNA release and transport through the nuclear pore
into the nucleus. The HSV-1 ts mutant tsB7 is completely blocked for viral gene expression at the
nonpermissive temperature (NPT) (278) because it is defective for the release of DNA from capsids
at the NPT (21). The ts mutation in tsB7 maps in the VP1/2 gene (21), suggesting that this large
tegument protein plays a role in DNA release at the nuclear pores. These results also suggest that
the VP1/2 tegument protein is transported to the nuclear pore with the capsid; nevertheless, it is
still conceivable that the defective protein is unable to be released in the cytoplasm and thus is kept
artifactually with the nucleocapsid during transport through the cytoplasm and blocks uncoating at
the nuclear pore. Recent in vitro results have shown that binding of the capsid to the nuclear pores
is blocked by wheat germ agglutinin, antinuclear pore complex antibodies, or antibodies against
importin b ( 422). Thus, the available data suggest that the interaction of capsid–tegument
structures with the nuclear pore proteins causes a structural change in the former, with the
consequence that viral DNA is extruded from the capsids into the nucleus; however, the molecular
details remain to be defined. The presence of intact, empty capsids for at least 2 hours after
exposure of cells to the virus suggests that the extrusion of the DNA does not coincide with
complete dissociation of the capsid.

Beberapa fungsi dari protein tegument virus dan gen mengungkapkan setelah infeksi menunjukkan
bahwa lingkungan di dalam sel inang adalah jelas bermusuhan dengan virus yang masuk. Protein
tegument dimasukkan ke dalam sel bersamaan dengan kapsid, dan beberapa memainkan peran
kunci dalam menciptakan lingkungan yang memungkinkan replikasi virus efisien. Meskipun fungsi
dari banyak protein tegument tetap sulit dipahami, tampak jelas bahwa distribusi mereka bervariasi
pada awal infeksi. Sebagai contoh, dua protein, VP16 dan UL41, dijelaskan secara rinci dalam bagian
berikutnya, tetapi mereka mempromosikan transkripsi gen dalam inti dan penutup sintesis protein
tuan rumah dalam sitoplasma, masing-masing. Kedua protein virion memainkan peran yang jelas
dalam mempersiapkan sel inang untuk replikasi virus yang efisien.

Table 1 lists a large number of viral proteins reported to be components of the viral tegument. With
the two exceptions listed previously, the functions of the tegument proteins are not readily
discernible, largely because many are either dispensable for viral replication or their function as
tegument proteins is different from that expressed in the course of productive infection after de
novo synthesis. For example, US11, genetically engineered to be expressed early in infection, blocks
the shutoff of protein synthesis induced by activated protein kinase R (PKR) ( 66). Virions carry about
2,000 copies of US11 protein; after infection, these are associated with polyribosomes and 60S
ribosomal subunits and do not block the shutoff of protein synthesis caused by activated PKR in cells
infected with g 134.5-negative mutants. Similarly, ICP22 and other a proteins are posttranslationally
modified by both the U L13 and US3 viral protein kinases. However, there is no evidence that ICP22
is modified by the viral kinases introduced into the infected cell as tegument proteins (421,471,472).
Thus, the functions of many of the tegument proteins remain to be identified. Nevertheless, the
process of entry and release of tegument proteins can be harmful to the cell because cells arrested
at the stage of release of tegument proteins can undergo apoptosis (176,700).

Nasib DNA virus pada Masuk ke Inti

The bulk of the incoming viral DNA circularizes rapidly after infection and in the absence of viral
protein synthesis (179,445), suggesting that under these conditions, circularization of the genome is
promoted by cellular proteins or viral proteins brought into the infected cell in the virion. It has been
suggested that the viral DNA ends are held together in the virion and are rapidly ligated by cellular
enzymes ( 445). Because viral DNA is nicked and contains ribonucleotides (see Genome Structure
and Organization), repair, circularization, and conversion to the appropriate conformation must then
take place. These events may explain the involvement of the RCC1 (regulator of chromosome
condensation) gene product in early events in viral infection reported by Umene and Nishimoto (
638), but this remains to be verified. It has also been suggested that circularization may result from
recombination between direct repeats in the terminal a sequences (37), consistent with the
hypothesis that fluctuation in the number of a sequences could be the consequence of
recombination between free ends (390). Such recombination events undoubtedly take place
because the number of such repeats varies within the DNA populations arising from a single plaque.
It is likely, however, that such recombination events also occur during viral DNA synthesis and
packaging.

Leinbach and Summers (317) reported that HSV DNA remains in a nonnucleosomal form during the
course of productive infection of cells.

Overview of Productive Infection Gene Expression

During productive infection, more than 80 HSV proteins are expressed in a highly regulated cascade
fashion ( Fig. 5) in a number of coordinately expressed groups of gene products (230), and several
viral proteins play a role in regulation of viral gene expression. Transcription of viral DNA takes place
in the nucleus, and as would be expected, all viral proteins are synthesized in the cytoplasm. The
host RNA polymerase II is responsible for transcription of all viral genes on the viral DNA during
infection (8,102), although viral gene products may modify its activity and structure. Very soon after
infection, about 2 to 4 hours postinfection (hpi) at a multiplicity of infection (MOI) of 10 to 20 or in
the absence of other de novo synthesized viral proteins, the viral a or immediate-early (IE) genes are
expressed. These consist of six proteins designated as ICP0, ICP4, ICP22, ICP27, ICP47, and US1.5.
Although transcription of a genes requires no prior viral protein synthesis, an HSV protein brought in
with the virion tegument, VP16 (also called aTIF and Vmw65), stimulates the transcription of the a
genes, as described later. Five of the six a gene products, including ICP4, ICP0, ICP27, ICP22, and

US1.5, stimulate E gene expression in at least some types of cells. As described later, HSV infection
inhibits host transcription, RNA splicing and transport, and protein synthesis to facilitate the
transition from cellular to viral gene expression.

ARA. 5. Skema representasi dari regulasi ekspresi gen HSV. panah terbuka dan diisi mewakili
peristiwa dalam siklus reproduksi yang mengubah ekspresi gen “on” dan “off,” masing-masing. 1.
Menghidupkan dari transkripsi gen oleh-TIF protein, ag dikemas dalam virion. 2. Autoregulasi dari
ekspresi gen. 3. Menghidupkan transkripsi b gen. 4. Menghidupkan dari g transkripsi gen oleh dan
gen b produk melalui transactivation gen g, rilis gen g dari penindasan, dan replikasi DNA virus.
Perhatikan bahwa gen g berbeda sehubungan dengan ketatnya persyaratan untuk sintesis DNA.
heterogenitas yang ditampilkan sebagai kontinum di mana inhibitor sintesis DNA virus yang terbukti
memiliki efek minimal terhadap ekspresi gen ga tapi benar-benar menghalangi ekspresi gen gz. 5.

Expression of the next set of HSV genes, the b or early genes, requires at least the presence of
functional ICP4 but not the onset of viral DNA synthesis. Between about 4 to 8 hpi, the b proteins are
expressed at peak rates. Among these are proteins involved in replication of the viral DNA and
nucleotide metabolism. These viral proteins promote viral DNA replication, and expression of g, or
late, genes is then stimulated. Two general groups of b proteins have been identified, although rigid
criteria for classification into the two groups have not been defined. The b1 genes are expressed
within a short time after or almost concurrently with the onset of synthesis of a proteins and are
exemplified by UL29 encoding ICP8, the single-stranded protein, and UL39 encoding ICP6, the large
subunit of ribonucleotide reductase. The b 2 genes are expressed with more delay after a protein
expression and are exemplified by UL23 encoding thymidine kinase. Some of the b genes require
ICP27 for their expression, and this may correlate with the later kinetics characteristic of b 2 genes.

The g, or late, genes are expressed at peak times after viral DNA synthesis has commenced, and their
expression is enhanced by viral DNA synthesis. They have been lumped for convenience into two
groups, one called g 1, early-late, or leaky-late, and one called g2, late, or true-late, although in
reality, they form a continuum differing in their timing and dependence on viral DNA synthesis for
expression (98,101,259,565,651). The typical g1 gene (e.g., the genes encoding ICP5, gB, gD, and
ICP34.5) is expressed relatively early in infection and is stimulated a few fold by viral DNA synthesis.
The relatively abundant major capsid protein ICP5 is made both early and late in infection. In
contrast, typical g 2 genes (e.g., UL44, the gene encoding gC, UL41, UL36, UL38, and US11) are
expressed late in infection and are not expressed in the presence of effective concentrations of
inhibitors of viral DNA synthesis.

Berdasarkan pengetahuan kita yang terbatas tentang struktur promotor dan peraturan daerah gen
HSV saat ini, tampaknya ada perbedaan dalam organisasi umum promotor dan urutan peraturan gen
yang khas di masing-masing kelas (Gbr. 6). Secara umum, promotor gen mengandung berbagai situs
mengikat faktor transkripsi seluler (lihat Gambar. 6, ICP4 gen) hulu dari kotak TATA. Para promotor b
gen sejauh dipelajari mengandung situs mengikat untuk dua atau tiga faktor transkripsi selular hulu
dari situs start transkripsi (lihat Gambar. 6, gen TK). Para promotor gen g1 hanya berisi satu atau dua
situs hulu mengikat (lihat Gambar. 6, gen ICP5), sedangkan promotor g2 terdiri dari kotak TATA,
elemen inisiator, dan elemen penggerak hilir, yang masing-masing dapat bervariasi dari seluler
homolognya (lihat Gambar. 6, gC atau gen UL44). Tingkat transkripsi gen virus meningkatkan secara
umum untuk kelas kemudian kinetik gen (699), mungkin karena sejumlah besar protein akhir yang
dibutuhkan untuk perakitan virion. Tingkat peningkatan transkripsi tampaknya karena peningkatan
jumlah template yang dan modifikasi virus yang disebabkan dari aparat transkripsi yang beroperasi
pada molekul DNA virus.

ARA. 6. Diagram dari struktur prototypic promotor gen HSV. Promotor dan peraturan urutan
prototypic

gen dari a, b, g1, dan kelas kinetik g2 yang digambarkan.

We would like to emphasize that although there are prototype genes that allow the definition of
four post-a classes of genes, there is likely to be a continuum of genes from b2 to g1 genes, in terms
of their kinetics and requirements for viral gene expression. First, b and g gene expression in the
context of the viral genome requires the participation of five of the six a proteins: ICP0 (528), ICP4
(279,456), ICP27 (527), ICP22 (454,547), and US1.5 (421). Only a few viral genes have been
completely characterized with regard to their requirement for these a proteins; thus, we do not
know how the requirement for these genes correlates with the kinetic classes already defined.
Second, the differences between b and g1 genes are difficult to quantify and are not perfectly
delineated. In principle, the expression of b genes is not augmented by the onset of DNA synthesis,
whereas the expression of g1 genes is reduced in the presence of inhibitors of DNA synthesis.
However, expression of some of the b genes is inhibited slightly by inhibitors of viral DNA synthesis
(639), whereas some g1 genes are expressed early and are affected only minimally by inhibitors of
DNA synthesis (e.g., gB) (478). Nevertheless, it is useful to consider b and g gene expression
separately while discussing events in the course of productive infection.

ORF O dan ORF P gen menyajikan sebuah kasus khusus. gen ini ditekan oleh ICP4 dan oleh karena itu
tidak diungkapkan selama infeksi produktif atau di hadapan ICP4 fungsional. gen ini telah ditunjuk
sebagai pra-a gen dalam pengakuan persyaratan khusus untuk ekspresi mereka (307).

Ekspresi dari Gen

Setelah masuk ke dalam inti sel, genom HSV, mungkin dalam bentuk melingkar, melokalisasi ke
intranuclear situs dekat